全文获取类型
收费全文 | 497篇 |
免费 | 11篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 1篇 |
基础医学 | 49篇 |
口腔科学 | 5篇 |
临床医学 | 13篇 |
内科学 | 58篇 |
皮肤病学 | 9篇 |
神经病学 | 88篇 |
特种医学 | 3篇 |
外科学 | 11篇 |
综合类 | 28篇 |
预防医学 | 11篇 |
眼科学 | 4篇 |
药学 | 186篇 |
中国医学 | 30篇 |
肿瘤学 | 14篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 21篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 5篇 |
2014年 | 27篇 |
2013年 | 35篇 |
2012年 | 52篇 |
2011年 | 52篇 |
2010年 | 53篇 |
2009年 | 33篇 |
2008年 | 27篇 |
2007年 | 16篇 |
2006年 | 22篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 10篇 |
2002年 | 10篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 14篇 |
1998年 | 11篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1975年 | 2篇 |
1909年 | 1篇 |
排序方式: 共有511条查询结果,搜索用时 15 毫秒
1.
The serotonin-3 (5-HT3) agonist 1-phenylbuguanide (0.1–1.0 mM in perfusate) caused a robust, dose-dependent enhancement of extracellular dopamine content in nucleus accumbens as measured by in vivo microdialysis. This action was antagonized by co-perfusion of the 5-HT3 antagonists zacopride and GR38032F (1 mM in perfusate). Similar effects were observed in 5-HT-denervated rats. These findings suggest that there is a potent modulation of dopamine (DA) release in the nucleus accumbens mediated via 5-HT3 receptors, which appear to be located presynaptically on DA terminals of the mesolimbic DA pathway. 相似文献
2.
Site-directed mutagenesis of the human 5-HT1B receptor was performed to investigate the role of the amino acid residues cysteine 326 and tryptophan 327 in transmembrane region VI and aspartic acid 352 in transmembrane region VII in ligand binding. Binding studies were performed with the antagonist radioligand [3H]GR125743 on mutant and wild-type receptors stably expressed in Chinese hamster ovary cells (CHO)-K1 cells. Substitution of tryptophan 327 by alanine resulted in decreased affinities of all ligands tested. The most prominent changes in affinity were observed for the antagonist methiothepin and the antimigraine drug sumatriptan, which were reduced approximately 300- and 60-fold, respectively. Nevertheless, the affinity of 5-HT remained the same. Replacement of the aspartic acid 352 by alanine reduced high-affinity binding of 5-HT. Substitution of cysteine 326 by alanine had minor effects on ligand binding. Some of these results agree with the results from mutagenesis studies of the corresponding amino acids in other receptors. However, some notable differences also emerge showing that functional roles of individual amino acid residues must be tested experimentally in each receptor subtype. 相似文献
3.
糖皮质激素受体--虚证相关蛋白之一? 总被引:5,自引:0,他引:5
以已有实验与临床研究为依据,提出糖皮质激素受体(GR)是虚证相关蛋白之一的理论假说。分析了进一步深入研究论证的途径:①改进糖皮质激素受体检测方法;②应用酵母双杂交检测技术,了解GRβ与GRα之间的相互作用,并分析这些作用特征与阴虚、阳虚之间的关系;②运用良好的前瞻性设计,对临床虚证患者进行大量、反复的检测观察与统计分析。指出对该假说的研究论证,很有可能在蛋白质(受体)水平为中医证的微观诊断提供一个符合中医基本理论,具有现代科学依据的检测指标,并有可能发现能上调GR含量的药物。 相似文献
4.
5.
《Expert opinion on investigational drugs》2013,22(12):1527-1545
The therapeutic and prophylactic use of glucocorticoids is widespread due to their powerful anti-inflammatory, antiproliferative and immunomodulatory activity. However, long-term use of these drugs can result in severe dose-limiting side effects. One of the most critical and debilitating side effects is osteoporosis, which leads to increased risk of fractures. Glucocorticoids damage bone through several different mechanisms. The search for novel glucocorticoids that have reduced side effects in bone and other tissues is being driven by the identification of new mechanisms of action of the glucocorticoid receptor. This may facilitate the detection of new, safer therapies with efficacies equivalent to currently prescribed steroids. 相似文献
6.
7.
8.
Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions. 相似文献
9.
The hinge region in androgen receptor control 总被引:2,自引:0,他引:2
Clinckemalie L Vanderschueren D Boonen S Claessens F 《Molecular and cellular endocrinology》2012,358(1):1-8
The region between the DNA-binding domain and the ligand-binding domain of nuclear receptors is termed the hinge region. Although this flexible linker is poorly conserved, diverse functions have been ascribed to it. For the androgen receptor (AR), the hinge region and in particular the (629)RKLKKL(634) motif, plays a central role in controlling AR activity, not only because it acts as the main part of the nuclear translocation signal, but also because it regulates the transactivation potential and intranuclear mobility of the receptor. It is also a target site for acetylation, ubiquitylation and methylation. The interplay between these different modifications as well as the phosphorylation at serine 650 will be discussed here. The hinge also has an important function in AR binding to classical versus selective androgen response elements. In addition, the number of coactivators/corepressors that might act via interaction with the hinge region is still growing. The importance of the hinge region is further illustrated by the different somatic mutations described in patients with androgen insensitivity syndrome and prostate cancer. In conclusion, the hinge region serves as an integrator for signals coming from different pathways that provide feedback to the control of AR activity. 相似文献
10.