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   281篇
  国内免费   35篇
  完全免费   106篇
医药卫生   422篇
  2016年   2篇
  2015年   6篇
  2014年   23篇
  2013年   21篇
  2012年   15篇
  2011年   56篇
  2010年   59篇
  2009年   50篇
  2008年   35篇
  2007年   27篇
  2006年   20篇
  2005年   15篇
  2004年   17篇
  2003年   19篇
  2002年   16篇
  2001年   10篇
  2000年   11篇
  1999年   8篇
  1998年   2篇
  1997年   2篇
  1996年   3篇
  1995年   2篇
  1992年   1篇
  1991年   1篇
  1989年   1篇
排序方式: 共有422条查询结果,搜索用时 78 毫秒
1.
Objective To invest the efficient method which can culture and induce embryonic stem cells to neuroeyte in vitro. Methods Isolate the blastula o f 3.5 d from BALB/c species mouse. Culture the cells from inner cell mass (inner cell mass, ICM) which were isolated by mechanical method on the mouse embryonic fibroblaste cell (MEF) feeder layer or 0.1% gelatin coated dishes. The stem ceils were identified by characterized morphology, alkaline phosphatase stain, differential potency in vivo and immunoehemistry stain. The isolated cells were differentiated by serial induction method that mimicking the intrinsic developmental process of the neural system. Results The isolated cells were positive for alkaline phosphatatse and SSEA-1 ( stage specific embryonic antigen 1 ). Moreover they were identified pluripotent by differentiation in vivo. Therefore the isolated ceils presented the characters of ESCs. Then the isolated cells were able to differentiate into neuroeytes in vitro. Conclusion Mouse embryonic stem ceils isolation, culture and differentiation system has been established.  相似文献   
2.
Li DB  Tang J  Fan XT  Song M  Xu HW  Bai Y 《神经科学通报》2006,22(1):52-57
Objective To identify the genetype of the PS1/APP double transgenie mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenie mice models and Aβ1-40-injeeted rats models of Alzheimer disease. Methods The modified congo red staining, Nissl's staining and immunohistology staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results ①The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. ②The Aβ1-40-intrahippocmnpal-injeeted rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl's staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Aβ1-40-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Aβ deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenie PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Aβ deposits and the spongiocyte response , while no neurons loss were observed in this model.  相似文献   
3.
Objective To study the developmental changes of glutamic acid decarboxylase-67 (GAD-67, a GABA synthetic enzyme) in normal and hypoxic ischemic (HI) brain. Methods C57/BL6 mice on postnatal day (P) 5, 9, 21and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD-67 was up regulated with brain development and significant difference was seen between mature (P21, P60) and immature (P5, P9) brain. GAD-67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia (HI) insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD-67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that (15.6 +/- 7.0)%TUNEL positive cells were GAD-67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.  相似文献   
4.
Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency (PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25 μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron .in the rat.  相似文献   
5.
Zhu ZH  Wang BR  Tan QR  Duan XL  Kuang F  Xu Z  Ju G 《神经科学通报》2006,22(3):144-150
Objective In order to characterize the feature of stress response induced by stressor with both physical and psychological natures, the effect of water restriction performed in different experimental modes on the physiological parameters, psychological behavioral manifestations and brain c-Fos expressions were observed and compared. Methods 58 male Wistar rats were used and randomly divided into three experimental groups (n=18 for each) and a control group (n=4). In control group, the rats were allowed to access drinking water freely at all experimental period. In the experimental groups the water supply to the rats was restricted. In timed water supply (TW) group, the water was supplied twice a day, 10 min for each in fixed hours every day. In empty bottle-served (EB) and water-restricted (WR) groups, the water was served only once a day for 10 min, either in the early morning or evening, and in the other time point scheduled for water supply only an empty bottle without water was provided in the EB group and nothing was given in the WR group. The quantities of drank water and eaten food, weight-gaining, and behavior score were observed every day. The serum level of corticosterone was assayed and the rats were sacrificed with fixative perfusion of 3 d, 7 d or 14 d respectively, following water restriction (n=6 for each time point in each group). The brain c-Fos expressions were examined with immunohistochemistry. Results The slowing down of weight-gaining, rise of serum corticosterone level, occurrence of psychological behavioral manifestations of unpeaceful restlessness such as exploring and attacking, enhance of c-Fos expression in the subfomical organ (SFO), median preoptic nucleus (MnPO), area postrema (AP), hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON), medial (MeA) and central (CeA) amygdaloid nucleus and ventrolateral septum (LSV) were noticed in both EB and WR groups, except the nucleus of solitary tract (NTS) in which the Fos expression was decreased. The changes of Fos expression in most of nuclei in EB group began at day 3, at least persisted till day 7, and backed down at day 14. While in WR group, similar changes started at day 7 and reached its peak at day 14. In TW group, only the concentration of corticosterone at day 7 was slightly increased and the rest indexes observed were unchanged. Conclusion The results indicate that water restriction induces physical as well as psychological stress responses. And the water restrictions experimentally executed in different modes result in different manifestations of behavioral response and brain immediately early gene expression in discrete brain nuclei/regions.  相似文献   
6.
Objective The potential of all central nervous system synapses to exhibit long term potentiation (LTP) or long term depression (LTD) is subject to modulation by prior synaptic activity, a higher-order form of plasticity that has been termed metaplasticity. This study is designed to examine the plasticity and metaplasticity in the lateral perforant path of rat. Methods Field potential was measured with different priming and conditioning stimulation protocols. Results Ten-hertz priming, which does not affect basal synaptic transmission, caused a dramatic reduction in subsequent LTP at lateral perforant path synapses in vitro, and the reduced LTP lasted for at least 2 h. The LTD was unaffected. The reduction of LTP in the lateral perforant path was also readily induced by applying priming antidromically at the mossy fibers. Conclusion Priming with 10 Hz, which is within a frequency range observed during physiological activity, can cause potent, long-lasting inhibition of LTP, but not LTD. This form of metaplasticity adds a layer of complexity to the activity-dependent modification of synapses within the dentate gyrus.  相似文献   
7.
Wang YF  Li CC  Cai JX 《神经科学通报》2006,22(5):274-280
目的 在脑老化和阿尔茨海默尔氏病人脑中,氧自由基的升高是其神经元发生退行性病变,从而导致突触可塑性和认知障碍的机制之一。本文研究了阿尼西坦(aniracetam,一种治疗老年痴呆的药物)对抗双氧水损伤神经元活力,线粒体电位及海马突触传递长时程增强(Long—term potentiation,LTP)的作用。方法 用四甲基偶氮唑盐(3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide,Mar)法测定神经元的活力,用线粒体荧光探针MitoTracker Red(CMX Ros)研究线粒体电位的变化,用膜片钳方法记录了海马CA1区的突触传递效能。结果 200μmol/L的双氧水明显损伤小鼠大脑皮层原代培养神经元的细胞活力,降低其线粒体电位,而10μmol/L或100μmol/L阿尼西坦预处理能明显对抗双氧水对细胞活力和线粒体电位的降低作用。双氧水在不影响基础突触传递的剂量下(20μmol/L),却能显著抑制海马LTP的诱导。阿尼西坦在100μmol/L剂量下,对基础突触传递没有明显影响,对正常小鼠脑片CA1区的LTP也没有易化作用,然而,100μmol/L的阿尼西坦却能显著地恢复由双氧水损伤的海马LTP。结论 本研究结果表明,阿尼西坦对双氧水导致的毒性具有较强的神经保护作用,这为临床上用其治疗神经退行性疾病提供了参考依据。  相似文献   
8.
Objective To explore the effects of exercise on dentate gyrus (DG) neurogenesis and the ability of learning and memory in hippocampus-lesioned adult rats. Methods Hippocampus lesion was produced by intrabippocampal microinjection of kainic acid (KA). Bromodeoxyuridine (BrdU) was used to label dividing cells. Y maze test was used to evaluate the ability of learning and memory. Exercise was conducted in the form of forced running in a motor-driven running wheel. The speed of wheel revolution was regulated at 3 kinds of intensity: lightly running, moderately running, or heavily running. Results Hippocampus lesion could increase the number of BrdU-labeled DG cells, moderately running after lesion could further enhance the number of BrdU-labeled cells and decrease the error number (EN) in Y maze test, while neither lightly running, nor heavily running had such effects. There was a negative correlation between the number of DG BrdU-labeled cells and the EN in the Y maze test after running. Conclusion Moderate exercise could enhance the DG neurogenesis and ameliorate the ability of learning and memory in hippocampus-lesioned rats.  相似文献   
9.
目的 探讨脆性X智能低下蛋白(fragile X mental retardation protein,FMRP)对微管相关蛋白1B(microtubuleassociated protein 1B,MAP1B)是否具有调控作用。方法应用免疫组化、免疫印记和原位杂交的方法,对1周龄和6周龄的Fmr1基因敲除型(KO)和同龄野生型(WT)小鼠脑组织MAP1B及MAP1B mRNA进行分析。结果免疫组化的结果显示 :6周龄KO小鼠各个脑区MAP1B的平均光密度值(MOD)值均显著低于同龄WT小鼠(P 〈 0.05),1周龄KO小鼠仅在小脑和海马显著降低(P 〈 0.01) ;各脑区MAP1B的MOD值在6周龄小鼠均比同基因型的1周龄小鼠显著降低(P 〈 0.05)。免疫印记和原位杂交结果分别显示MAP1B及MAP1B mRNA在KO小鼠的海马组织均显著降低(P 〈0.05)。结论MAP1B和MAP1B mRNA在Fmr1基因敲除小鼠脑组织的表达均显著减少,提示FMRP可能正性调节MAP1B的表达。  相似文献   
10.
目的探讨脑室内神经干细胞移植修复成年小鼠谷氨酸神经毒性损伤的可能性。方法从15日小鼠胚胎脑组织分离神经干细胞,采用免疫细胞化学技术检测细胞Nestin抗原表达;通过免疫荧光染色观察所移植神经干细胞在体内的存活及定位。除对照组外,所有小鼠均以谷氨酸单钠(每天4.0 g/kg)灌胃,连续10天。灌胃后第1 天和10 天,谷氨酸加神经干细胞移植组行神经干细胞脑室内移植(1× 105细胞 /鼠),对照组和谷氨酸组注射DMEM 液。末次移植后第 11天进行Y迷宫试验,试验结束后进行小鼠脑病理检查,以分析谷氨酸引起的脑功能和形态学上的改变。结果所分离细胞呈Nestin阳性表达;移植10天后所移植神经干细胞在小鼠脑中呈区域特异性存活;脑室内移植神经干细胞能明显促进成年小鼠脑谷氨酸兴奋性毒性损伤的修复。结论脑室内移植神经干细胞可用于疾病或损伤脑组织的修复。  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