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1.
Cell therapy with autologous donor‐specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor‐specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR‐Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor‐specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts. Tregs expressing an irrelevant or anti‐HLA‐A2‐specific CAR were administered to Bl/6 mice at the time of transplanting an HLA‐A2+ Bl/6 skin graft. Donor‐specific CAR‐Tregs, but not irrelevant‐CAR Tregs, significantly delayed skin rejection and diminished donor‐specific antibodies (DSAs) and frequencies of DSA‐secreting B cells. Donor‐specific CAR‐Treg–treated mice also had a weaker recall DSA response, but normal responses to an irrelevant antigen, demonstrating antigen‐specific suppression. When donor‐specific CAR Tregs were tested in HLA‐A2‐sensitized mice, they were unable to delay allograft rejection or diminish DSAs. The finding that donor‐specific CAR‐Tregs restrain de novo but not memory alloreactivity has important implications for their use as an adoptive cell therapy in transplantation.  相似文献   
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Introduction

Management of glioblastoma, with a very poor prognosis, remains a challenge in older patients because of coexisting comorbidities and the increased risk of toxic treatment effects. The use of screening tools to identify vulnerable patients is essential. This study was performed to establish whether the G8 scale can be used for screening older patients with glioblastoma.

Methods

We retrospectively reviewed the files of patients assessed by the G8 scale and diagnosed with glioblastoma at a single center from January 2010 to July 2017. Patients aged 65?years or older were classified into three groups (more efficiently than two groups) according to their G8 score to identify those with a poor prognosis: high score group, G8 score 14.5–17; intermediate score group, G8 score 10.5–14; and low score group, G8 score?<?10.5.

Results

Of 89 patients, 19% were classified into the high score group, 43% into the intermediate score group, and 38% into the low score group. Median overall survival was four months in the low score group, 15?months in the intermediate score group, and 42?months in the high score group (p?<?.0001). On multivariate analysis, G8 score was a significant independent predictor of overall survival (hazard ratio: 55.46; 99.5% confidence interval: 13.42–229.13; p?<?.0001).

Conclusions

Here, we highlighted the possibility of using the G8 score, with possibly three cut-offs, in the management of older patients with glioblastoma and determined the prognostic role of this quick and easy screening tool.  相似文献   
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Objective

To examine the utility of a patient-level information video as part of the contraception consultation visit. Specifically, to assess the impact of the video on women's contraception choice, and, further, to assess patient and provider acceptability of incorporating the video into the patient visit.

Methods

A pre-post study design was used to assess the impact on patients' contraceptive choices and knowledge. Participants (n?=?49) answered questions regarding contraceptive preferences and knowledge of long-acting reversible contraception (LARC), then watched a 12-minute patient-level counselling video that presented evidence-based information about contraception in descending order of effectiveness. Clinicians (n?=?39) also viewed the video and completed a survey. A retrospective chart review of 100 contraception visits was completed.

Results

Patient preference for IUDs increased significantly, whereas condoms decreased pre-to-post video (hormonal: 8.2% to 20.4%; copper: 0% to 16%; condoms: 32.7% to 18%, P?<?0.05). Although 74.4% of clinicians believed that the hormonal IUD was the “ideal” form of contraception when no contraindications were present, 95% stated that the oral contraceptive pill was most often prescribed, and a chart review revealed that the oral contraceptive pill was discussed at 88% of contraceptive counselling visits. Both patients and clinicians found the video useful and acceptable.

Conclusion

A patient-level contraceptive information video improved interest in LARC. Both patients and clinicians viewed the video as an acceptable addition to the contraceptive counselling visit.  相似文献   
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The article is based on a multidimensional conception of healthcare system performance. Our objectives are to assess the performance of the healthcare systems of 27 Organisation for Economic Co-operation and Development (OECD) countries and to discern the countries' profiles according to the homogeneity of their healthcare systems' levels of performance. The analyses were carried out on data collected from the 27 high-income OECD countries, primarily using the OECD Health Data 2007 database, the World Health Organization 2008 statistics, OECD Health at a Glance and OECD Social Indicators. Each healthcare system's performance was assessed on the basis of the volume of available resources, services produced and health outcomes achieved and efficiency, effectiveness and productivity, thus characterizing the investments made in proportion to the available resources and services produced. Overall performance profiles were constructed taking into account simultaneously the level of all these components. Using multiple clusters analysis, we were able to group the countries into four profiles (satisfactory, promising, weak-polarized and limited) according to the homogeneity of their performance levels. This article offers a broad overview of the performance of these healthcare systems. The results will enable decision-makers to know the strengths and weaknesses of their own health care system and also to compare it with those of other countries.  相似文献   
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Background and Aim: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti‐thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. Methods: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti‐thrombotic therapy. VCE studies were re‐evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti‐thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti‐thrombotic therapy was resumed before the VCE study. Results: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty‐two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti‐thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20–60.42, P = 0.032). Conclusions: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti‐thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.  相似文献   
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OBJECTIVE:

To describe the viral etiology and epidemiology of nosocomial viral gastroenteritis (NVG) at a tertiary care pediatric hospital and identify any changes over the past two decades.

METHODS:

Retrospective review of all patients with laboratory-confirmed NVG at The Hospital for Sick Children (Toronto, Ontario), from January 1, 2004, to December 31, 2005.

RESULTS:

One hundred forty-two episodes of NVG were found among 133 patients, occurring in 0.48 of 100 admissions. The median age was two years; 42% were <1 year of age and 41% were immunocompromised. The most commonly detected pathogen was torovirus (67% of episodes), followed by rotavirus (19%) and adenovirus (9%). Seventy-five cases (53%) were epidemiologically linked in 32 separate clusters (median cluster size two, range two to four). The NVG rate fell from 0.63 of 100 to 0.22 of 100 admissions after March 2005 (P<0.001) when enhanced infection control precautions were instituted in response to an outbreak of vancomycin-resistant Enterococcus.

CONCLUSIONS:

Torovirus remains the most commonly identified cause of NVG at The Hospital for Sick Children. Most NVG cases were epidemiologically linked, and a significant reduction in cases occurred after the institution of enhanced infection control practices following an outbreak of vancomycin-resistant Enterococcus. Improved education and surveillance for NVG should lead to further reduction in this problem.  相似文献   
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