首页 | 官方网站   微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1780篇
  国内免费   28篇
  完全免费   48篇
医药卫生   1856篇
  2015年   13篇
  2014年   75篇
  2013年   74篇
  2012年   93篇
  2011年   160篇
  2010年   105篇
  2009年   132篇
  2008年   117篇
  2007年   80篇
  2006年   129篇
  2005年   88篇
  2004年   76篇
  2003年   76篇
  2002年   59篇
  2001年   54篇
  2000年   45篇
  1999年   43篇
  1998年   28篇
  1997年   29篇
  1996年   22篇
  1995年   27篇
  1994年   18篇
  1993年   19篇
  1992年   14篇
  1991年   22篇
  1990年   17篇
  1989年   15篇
  1988年   9篇
  1987年   14篇
  1986年   20篇
  1985年   22篇
  1984年   30篇
  1983年   28篇
  1982年   28篇
  1981年   13篇
  1980年   15篇
  1979年   16篇
  1978年   5篇
  1977年   4篇
  1976年   8篇
  1975年   1篇
  1974年   1篇
  1973年   4篇
  1972年   7篇
  1968年   1篇
排序方式: 共有1856条查询结果,搜索用时 78 毫秒
1.
BACKGROUND: Valproic acid (VPA) may induce hyperammonemic encephalopathy. On the other hand, seizure-inducing effects of antiepileptic drugs (AEDs) may be a paradoxical reaction or a result of AED-induced encephalopathy (commonly induced by VPA). METHODS: We present the case of a 19-year-old male who developed acute mental status changes consistent with encephalopathy evolving into repetitive seizures with oral automatisms induced by relatively small doses of VPA. RESULTS: Although serum hepatic enzymes, such as AST and ALT, were normal, serum ammonia concentration was high, i.e. 70 micromol/l (normal range 9-33 micromol/l). Administration of VPA was discontinued immediately after admission. The patient's condition improved during the second week of hospitalization and ammonium levels returned to normal. CONCLUSION: In conclusion, although uncommon, a possible induction of non-convulsive status epilepticus by valproate-induced hyperammonemic encephalopathy should be taken into account and properly managed by discontinuation of the drug.  相似文献   
2.
Zaccara G  Franciotta D  Perucca E 《Epilepsia》2007,48(7):1223-1244
Idiosyncratic drug reactions may be defined as adverse effects that cannot be explained by the known mechanisms of action of the offending agent, do not occur at any dose in most patients, and develop mostly unpredictably in susceptible individuals only. These reactions are generally thought to account for up to 10% of all adverse drug reactions, but their frequency may be higher depending on the definition adopted. Idiosyncratic reactions are a major source of concern because they encompass most life-threatening effects of antiepileptic drugs (AEDs), as well as many other reactions requiring discontinuation of treatment. Based on the underlying mechanisms, idiosyncratic reactions can be differentiated into (1) immune-mediated hypersensitivity reactions, which may range from benign skin rashes to serious conditions such as drug-related rash with eosinophilia and systemic symptoms; (2) reactions involving unusual nonimmune-mediated individual susceptibility, often related to abnormal production or defective detoxification of reactive cytotoxic metabolites (as in valproate-induced liver toxicity); and (3) off-target pharmacology, whereby a drug interacts directly with a system other than that for which it is intended, an example being some types of AED-induced dyskinesias. Although no AED is free from the potential of inducing idiosyncratic reactions, the magnitude of risk and the most common manifestations vary from one drug to another, a consideration that impacts on treatment choices. Serious consequences of idiosyncratic reactions can be minimized by knowledge of risk factors, avoidance of specific AEDs in subpopulations at risk, cautious dose titration, and careful monitoring of clinical response.  相似文献   
3.
Amark P  Stödberg T  Wallstedt L 《Epilepsia》2007,48(5):1023-1024
Vagus nerve stimulation (VNS) is widely used to treat refractory epilepsy. It is usually safe and has few side effects. Cardiac arrhythmia has been reported during lead tests performed during implantation of the device, but never during regular treatment. We report here a case where vagally induced bradyarrhythmia, perfectly correlated with the stimulation periods, suddenly occurred two years and four months after the VNS implantation. The diagnosis was based on the appearance of syncope-like episodes. No specific cause could be found to explain the appearance of the episodes. To our knowledge, this is the first report on this severe and life-threatening side effect of VNS and should alert clinicians to its possibility. However, considering the large number of VNS implantations performed worldwide, it must be regarded as an extremely rare complication.  相似文献   
4.
PURPOSE: The Liverpool Adverse Events Profile (LAEP) is used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). This study evaluated LAEP in newly diagnosed seizure patients, and examined the relation between LAEP, anxiety, and depression. METHODS: Seizure patients seen in the two First Seizure Clinics were categorized into group A (AEDs commenced after assessment), group B (AEDs commenced before assessment), and group C (no AEDs). LAEP and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline (n=164) and 3 months (n=103). Each LAEP symptom was assessed for baseline frequency, 3-month frequency, and frequency change over a 3-month period. Global scores for LAEP and HADS were analysed at baseline and 3 months. RESULTS: Symptom-reporting patterns were similar between groups. However, increased frequency over a 3-month period occurred for 12 symptoms in group A, 10 in group B, and one in group C. Global LAEP and HADS showed no significant group differences at baseline or changes over a 3-month period. Multiple regression revealed that HADS scores predicted LAEP global scores better than did AED status. Multivariate analyses of variance demonstrated that increased reporting of 16 of 19 LAEP symptoms was significantly related to higher anxiety and depression rates. CONCLUSIONS: In a First Seizure Clinic, LAEP detects changes in specific symptom frequencies when used as a repeated, symptom-by-symptom measure. Increased symptom frequency is associated with diagnostic category/AED treatment, anxiety, and depression. Global LAEP scores do not illustrate differences in symptom reporting between patients.  相似文献   
5.
Purpose: To determine whether low-frequency, 1-Hz sine-wave stimulation (LFS) applied to a fully kindled amygdala focus would show antiepileptic properties in rats that were either naturally seizure prone (Fast) or seizure resistant (Slow). Methods: Normal twisted and/or "spanning" bipolar electrode configurations were implanted in the amygdalae of adult male Fast and Slow rats. In experiment one, rats were kindled daily to stage-5 levels through one electrode type until stable afterdischarge thresholds (ADTs) were obtained. Next, LFS was applied through the kindled electrode, and ADTs were redetermined 1 min later, and daily for a week, without reapplying the LFS. In experiment two, a single, normal bipolar kindling electrode was implanted in the amygdala and centered between two poles of a spanning electrode. After stable kindled ADTs were obtained, LFS was applied to the amygdala "area" through the spanning electrode. ADTs were redetermined at the kindled electrode as earlier. Results: LFS through the kindling electrode had no effect on ADTs 1 min later, but the ADTs increased dramatically 24 h later and then slowly returned to baseline over days. In experiment two, LFS applied through the nonkindled spanning electrode also showed a small but significant threshold elevation at the interposing kindled electrode. Importantly, no obvious neuropathology was associated with these LFS treatments. Conclusions: LFS applied directly to the kindled network has significant threshold-elevating properties that are less evident when applied to the "general area"; here LFS must be delivered through a larger surface area and/or at higher intensity.  相似文献   
6.
Schaub C  Uebachs M  Beck H 《Epilepsia》2007,48(7):1339-1350
PURPOSE: A substantial proportion of epilepsy patients ( approximately 30%) continue to have seizures despite carefully optimized treatment with antiepileptic drugs (AEDs). One key concept to explain the development of pharmacoresistance is that epilepsy-related changes in the properties of CNS drug targets result in AED-insensitivity of these targets. These changes then contribute to drug-resistance on a clinical level. We have tested this hypothesis in hippocampal CA1 neurons in experimental epilepsy. METHODS: Using patch-clamp techniques, we thoroughly examined the effects of carbamazepine (CBZ) and phenytoin (PHT) on voltage-gated Na(+) currents (I(Na)) in hippocampal CA1 neurons of sham-control and chronically epileptic rats. RESULTS: We find that there were significant changes in the effects of PHT, but not CBZ on the voltage-dependence of inactivation, resulting in a significant reduction in voltage-dependent blocking effects in chronically epileptic animals. Conversely, CBZ effects on the time course of recovery from inactivation of I(Na) were significantly less pronounced in epileptic compared to sham-control animals, whereas PHT effects remained unaltered. CONCLUSIONS: Our findings indicate that AED-sensitivity of Na(+) currents is reduced in chronic epilepsy. The reduction in sensitivity is due to different biophysical mechanisms for CBZ and PHT. Furthermore, comparison to published work suggests that the loss of AED-sensitivity is less pronounced in CA1 neurons than in dentate granule neurons. Thus, these results suggest that target mechanisms of drug resistance are cell type and AED specific. Unraveling these complex mechanisms is likely to be important for a better understanding of the cellular basis of drug-resistant epilepsy.  相似文献   
7.
8.
Mula M  Trimble MR  Sander JW 《Epilepsia》2007,48(12):2322-2326
PURPOSE: To investigate the hypothesis that some patients with epilepsy are generally prone to develop psychiatric adverse events (PAEs) during antiepileptic drug (AED) therapy irrespective of the mechanism of action of the drugs. METHODS: From a large case registry of patients prescribed topiramate (TPM) and levetiracetam (LEV), data of patients who had a trial with both drugs were analyzed. Demographic and clinical variables of those who developed PAEs with both drugs (group 1) were compared with those who did not (group 2). Subsequently, from the whole case registry, psychopathological features, demographic, and clinical variables of patients developing PAEs with TPM were compared with those of patients developing PAEs with LEV. RESULTS: The case registry included over 800 patients. Among 108 patients having a trial with both drugs, we identified 9 patients in group 1 and 71 in group 2. Previous psychiatric history, family psychiatric history and history of febrile convulsions showed to be significant clinical correlates. Comparing patients who developed PAEs with LEV with those who developed PAEs with TPM, there were no differences in epilepsy related variables. Well-defined DSM-IV disorders were more frequent with TPM than with LEV. Seizure freedom was associated with psychosis. Conclusions: This study suggests that a subgroup of patients is generally prone to develop PAEs during AED therapy, despite different pharmacological properties of the AEDs. A particular clinical profile and relevant variables have been identified.  相似文献   
9.
Intellectual and language functions in children of mothers with epilepsy   总被引:1,自引:0,他引:1  
Thomas SV  Sukumaran S  Lukose N  George A  Sarma PS 《Epilepsia》2007,48(12):2234-2240
PURPOSE: To compare the intellectual and language functions of children of mothers with epilepsy (CME) with that of controls matched for age and socioeconomic status. METHODS: Cases were CME, aged six years or more (n = 71), drawn from a prospective cohort in the Kerala Registry of Epilepsy and Pregnancy. Controls were 201 children of parents without epilepsy, matched for age and socioeconomic status. The outcome measures included Indian adaptation of Wechsler Intelligence Scale for children and MLT-a locally developed proficiency test for regional language. All relevant data were abstracted from the registry records. RESULTS: The Full Scale IQ and MLT scores were significantly lower for the cases (87.7 +/- 22.6 and 73.4 +/- 17.3) compared to controls (93.0 +/- 14.4 and 83.2 +/- 11.8). Compared to controls, CME scored poor on all subtests of MLT but their impairment was confined to only some of the subtests of IQ. Maternal education and maternal IQ significantly correlated with low IQ and MLT scores for CME whereas type of epilepsy, seizures during pregnancy or low birth weight did not have any significant association with these outcome measures. Polytherapy and higher dosage of antiepileptic drugs (AEDs) were associated with significant impairment in outcome measures. Infants with low developmental quotient at one year of age continued to have low scores on outcome measures at six years. CONCLUSIONS: Low maternal IQ, maternal education, and antenatal AED exposure were associated with significant impairment of intellectual and language functions for CME at six years.  相似文献   
10.
Summary:  Purpose: We observed three apparently unrelated and geographically separate Arab families with Lafora disease in Israel and the Palestinian territories.
Methods: We clinically evaluated the families and analyzed their DNA for EPM2A mutations.
Results: Of seven individuals with Lafora disease, the clinical onset varied from 13 to 20 years. All three families shared the same novel homozygous deletion in EPM2A . Haplotype analysis around the deletion showed that the families shared a common homozygous haplotype. The boundaries of this haplotype varied between families and even within one family.
Conclusions: We conclude that considerable variability in the age at onset of Lafora disease can occur within families. Identical mutations can be associated with the classic adolescent presentation, as well as late-onset cases. Haplotype analysis suggests that this EPM2A mutation arose many generations previously, so it may be of importance for cases distributed more widely in the Middle East.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号