全文获取类型
收费全文 | 211篇 |
免费 | 11篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 15篇 |
妇产科学 | 1篇 |
基础医学 | 26篇 |
口腔科学 | 9篇 |
临床医学 | 15篇 |
内科学 | 16篇 |
皮肤病学 | 5篇 |
神经病学 | 22篇 |
特种医学 | 6篇 |
外科学 | 4篇 |
综合类 | 7篇 |
预防医学 | 10篇 |
眼科学 | 9篇 |
药学 | 74篇 |
中国医学 | 1篇 |
肿瘤学 | 1篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 4篇 |
2013年 | 10篇 |
2012年 | 26篇 |
2011年 | 25篇 |
2010年 | 17篇 |
2009年 | 4篇 |
2008年 | 19篇 |
2007年 | 18篇 |
2006年 | 11篇 |
2005年 | 12篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 9篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
排序方式: 共有222条查询结果,搜索用时 15 毫秒
51.
Objective: There have been innumerable advances in the pharmacotherapy of schizophrenia, but problems have emerged hand‐in‐glove, such as the presence of treatment‐emergent glucose intolerance and frank diabetes mellitus (DM). Method: Medication‐naïve patients with schizophrenia (n = 99) underwent baseline fasting and 2 h post‐prandial plasma glucose measurements repeated after 6 weeks after randomization to receive olanzapine, risperidone or haloperidol. The results were compared with a matched healthy control group. Results: A significant difference (P = 0.002) in baseline 2 h post‐prandial blood sugar (PPBS) was noted between the control group and the treatment group along with a significant increase in weight (P < 0.001), fasting blood sugar (P = 0.01) and 2 h PPBS (P < 0.001) from baseline to endpoint between the groups. A statistical significance in the incidence of DM at endpoint by the WHO criteria (10.1%) was also noted. Conclusion: Male patients with schizophrenia are liable to develop DM. Antipsychotic treatment leads to the development of DM in a significant 10.1% within 6 weeks. 相似文献
52.
Colubrid snake venoms potentially represent a vast source of novel biological actives and structural motifs owing to their diverse phylogeny. The present study describes the identification of rufoxin, a neurotoxin from the venom of Rhamphiophis oxyrhynchus (Rufous beaked snake) which is a member of the African colubrid lineage, the psammophiines. Rufoxin (1 microM) displayed reversible post-synaptic neurotoxic activity as evidenced by significant inhibition of indirect twitches and responses to exogenous nicotinic agonists in the chick biventer cervicis nerve-muscle preparation. Rufoxin (0.1-1.0 microM) also caused a rightward parallel shift of cumulative concentration-response curves to carbachol (CCh; 0.6-80 microM) without a significant depression of the maximum response, suggestive of classical competitive antagonism at the skeletal muscle nicotinic receptor. Rufoxin lacks NH(2)-terminal sequence homology to previously identified snake venom toxins. This work indicates a wider distribution of neurotoxins across the advanced snake superfamily than previously described. 相似文献
53.
Snake venom toxins have evolved to affect many prey physiological systems including hemostasis and thrombosis. These toxins belong to a diverse array of protein families and can initiate or inhibit multiple stages of the coagulation pathway or platelet aggregation with incredible specificity. Such specificity toward vertebrate molecular targets has made them extremely useful for diagnosis of human diseases or as molecular scalpels in physiological studies. The large number of yet-to-be characterized venoms provides a vast potential source of novel toxins and subsequent cardiovascular therapeutics and diagnostic agents. 相似文献
54.
55.
56.
57.
58.
59.
60.
Structure–function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms 总被引:1,自引:0,他引:1
R. Manjunatha Kini 《Toxicon》2005,45(8):1147
Phospholipase A2 (PLA2) enzymes from snake venom are toxic and induce a wide spectrum of pharmacological effects, despite similarity in primary, secondary and tertiary structures and common catalytic properties. Thus, the structure–function relationships and the mechanism of this group of small proteins are subtle, complex and intriguing challenges. This review, taking the PLA2 enzymes from spitting cobra (Naja nigricollis) venom as examples, describes the mechanism of anticoagulant effects. The strongly anticoagulant CM-IV inhibits both the extrinsic tenase and prothrombinase complexes, whereas the weakly anticoagulant PLA2 enzymes (CM-I and CM-II) inhibit only the extrinsic tenase complex. CM-IV binds to factor Xa and interferes in its interaction with factor Va and the formation of prothrombinase complex. In contrast, CM-I and CM-II do not affect the formation of prothrombinase complex. In addition, CM-IV inhibits the extrinsic tenase complex by a combination of enzymatic and nonenzymatic mechanisms, while CM-I and CM-II inhibit by only enzymatic mechanism. These functional differences explain the disparity in the anticoagulant potency of N. nigricollis PLA2 enzymes. Similarly, human secretory enzyme binds to factor Xa and inhibits the prothrombinase complex. We predicted the anticoagulant region of PLA2 enzymes using a systematic and direct comparison of amino acid sequences. This region between 54 and 77 residues is basic in the strongly anticoagulant PLA2 enzymes and neutral or negatively charged in weakly and non-anticoagulant enzymes. The prediction is validated independently by us and others using both site directed mutagenesis and synthetic peptides. Thus, strongly anticoagulant CM-IV binds to factor Xa (its target protein) through the specific anticoagulant site on its surface. In contrast, weakly anticoagulant enzymes, which lack the anticoagulant region fail to bind specifically to the target protein, factor Xa in the coagulation cascade. Thus, these studies strongly support the target model which suggests that protein–protein interaction rather than protein–phospholipid interaction determines the pharmacological specificity of PLA2 enzymes. 相似文献