全文获取类型
收费全文 | 386篇 |
免费 | 38篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 4篇 |
妇产科学 | 2篇 |
基础医学 | 138篇 |
口腔科学 | 4篇 |
临床医学 | 14篇 |
内科学 | 96篇 |
皮肤病学 | 3篇 |
神经病学 | 32篇 |
特种医学 | 7篇 |
外科学 | 10篇 |
综合类 | 18篇 |
预防医学 | 10篇 |
眼科学 | 2篇 |
药学 | 51篇 |
中国医学 | 6篇 |
肿瘤学 | 36篇 |
出版年
2024年 | 1篇 |
2023年 | 14篇 |
2022年 | 20篇 |
2021年 | 20篇 |
2020年 | 19篇 |
2019年 | 19篇 |
2018年 | 17篇 |
2017年 | 10篇 |
2016年 | 22篇 |
2015年 | 32篇 |
2014年 | 35篇 |
2013年 | 30篇 |
2012年 | 18篇 |
2011年 | 27篇 |
2010年 | 17篇 |
2009年 | 19篇 |
2008年 | 18篇 |
2007年 | 13篇 |
2006年 | 8篇 |
2005年 | 10篇 |
2004年 | 16篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2001年 | 7篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
排序方式: 共有434条查询结果,搜索用时 31 毫秒
21.
22.
23.
Chen Davidovich Matthew Belousoff Anat Bashan Ada Yonath 《Research in microbiology》2009,160(7):487-492
Structural analysis supported by biochemical, mutagenesis and computational evidence, revealed that the contemporary ribosome's active site is a universal symmetrical pocket made of ribosomal RNA. This pocket seems to be the remnant of the proto-ribosome, a dimeric RNA assembly evolved by gene duplication, capable of autonomously catalyzing peptide bond formation and non-coded amino acid polymerization. 相似文献
24.
Alexandre Huber Bernd Bodenmiller Aino Uotila Michael Stahl Stefanie Wanka Bertran Gerrits Ruedi Aebersold Robbie Loewith 《Genes & development》2009,23(16):1929-1943
The target of rapamycin complex 1 (TORC1) is an essential multiprotein complex conserved from yeast to humans. Under favorable growth conditions, and in the absence of the macrolide rapamycin, TORC1 is active, and influences virtually all aspects of cell growth. Although two direct effectors of yeast TORC1 have been reported (Tap42, a regulator of PP2A phosphatases and Sch9, an AGC family kinase), the signaling pathways that couple TORC1 to its distal effectors were not well understood. To elucidate these pathways we developed and employed a quantitative, label-free mass spectrometry approach. Analyses of the rapamycin-sensitive phosphoproteomes in various genetic backgrounds revealed both documented and novel TORC1 effectors and allowed us to partition phosphorylation events between Tap42 and Sch9. Follow-up detailed characterization shows that Sch9 regulates RNA polymerases I and III, the latter via Maf1, in addition to translation initiation and the expression of ribosomal protein and ribosome biogenesis genes. This demonstrates that Sch9 is a master regulator of protein synthesis. 相似文献
25.
26.
目的:探讨乳腺单纯癌临床诊断的量化标准。方法:对20例中期和20例晚期乳腺单纯癌癌细胞粗面内质网、游离核糖体、多核糖体的7个形态参数进行体视学分析,用逐步判别分析法剔选各参数值,建立判别函数。结果:Vvr2、Svr2、SR与Sr2之间有显著性差异(P<0.01),回代判别正确率达到85.7%。结论:本研究建立的乳腺单纯癌临床诊断量化标准对鉴别诊断乳腺癌及判断其恶性程度和预后具有重要意义。 相似文献
27.
《Annals of medicine》2013,45(4):302-311
AbstractIntroduction. We have studied the functions of truncated apoE4 forms in vitro and in vivo in order to identify the domains of apoE4 required for the biogenesis of apoE-containing high-density lipoprotein (HDL). Results. We have found that apoE4-185, -202, -229, or -259 could promote ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux in vitro, although less efficiently than Full-length apoE4, and had diminished capacity to activate lecithin cholesterol acyltransferase (LCAT). Formation of HDL in vivo was assessed by various methods following gene transfer in apolipoprotein A-I?/? × apoE?/? mice. Fast protein liquid chromatography of plasma showed that the truncated apoE forms, except apoE4-185, generated an apoE-containing HDL peak. Two-dimensional gel electrophoresis of plasma and electron microscopy showed that truncated apoE forms generated distinct HDL subpopulations and formed discoidal HDL particles which could be converted to spherical by co-administration of truncated apoE4-202 and LCAT. Conclusion. Overall, the in-vivo and in-vitro data are consistent and indicate that apoE4-185 is the shortest truncated form that supports formation of discoidal apoE4-containing HDL particles. 相似文献
28.
Marco Fischer Glenn R. Bantug Sarah Dimeloe Patrick M. Gubser Anne‐Valérie Burgener Jasmin Grählert Maria L. Balmer Leyla Develioglu Rebekah Steiner Gunhild Unterstab Ursula Sauder Gideon Hoenger Christoph Hess 《European journal of immunology》2018,48(10):1632-1643
The role of mitochondrial biogenesis during naïve to effector differentiation of CD8+ T cells remains ill explored. In this study, we describe a critical role for early mitochondrial biogenesis in supporting cytokine production of nascent activated human naïve CD8+ T cells. Specifically, we found that prior to the first round of cell division activated naïve CD8+ T cells rapidly increase mitochondrial mass, mitochondrial respiration, and mitochondrial reactive oxygen species (mROS) generation, which were all inter‐linked and important for CD8+ T cell effector maturation. Inhibition of early mitochondrial biogenesis diminished mROS dependent IL‐2 production – as well as subsequent IL‐2 dependent TNF, IFN‐γ, perforin, and granzyme B production. Together, these findings point to the importance of mitochondrial biogenesis during early effector maturation of CD8+ T cells. 相似文献
29.
目的探讨过氧化物酶体增殖物激活受体辅激活因子1α(PGC-1α)对高糖诱导的血管内皮细胞内活性氧簇(ROS)生成的影响。方法将人脐带静脉内皮细胞(HUVECs)分成对照组、空病毒Ad组、d-PGC-1α感染组、PGC-1αsiRNA转染组,分别将四组细胞置于正常糖及高糖环境中进行培养。用活性氧检测试剂盒处理标本,以酶标仪检测细胞内荧光强度,显示细胞内ROS浓度。结果高糖组HUVECs内ROS浓度明显高于正常糖组(P〈0.01);与对照组及空病毒Ad组比较,d-PGC-1α感染组ROS浓度明显降低,PGC-1αsiRNA转染组明显升高(P均〈0.01)。结论与正常糖组比较,高糖组HUVECs内ROS浓度明显升高;过度表达PGC-1α蛋白后,HUVECs内ROS浓度明显降低;抑制细胞内PGC-1α蛋白表达,则HUVECs内ROS浓度明显升高。提示PGC-1α可作为防治糖尿病血管并发症的新靶点之一。 相似文献
30.
RIO-2 kinase is known to regulate ribosome biogenesis and other cell cycle events. The 3D model of ATP bound and an unbound form of PFD0975w was generated using AfRIO-2 crystal structure 1TQI, 1ZAO as template employing Modeller9v7 program. Structural characterization identified N-terminal winged helix domain (1-84), C-terminal kinase domain (148-275), and presence of other critical residues known for ATP binding and kinase activity. Using Q-site and pocket finder, a number of well-defined substrate (peptide) binding regions were identified in the catalytic core of the protein. The peptide binding regions were further validated by molecular modeling a non-specific polyalanine peptide and a sequence-specific peptide2 into these sites to generate a stable PFD0975w/peptide complexes. Peptide fits well into identified pocket on PFD0975w and makes extensive interaction with the protein residues. These newly identified peptide binding sites potentially give opportunity to design a specific inhibitor against PFD0975w. There are subtle but significant differences between Plasmodium falciparum and human RIO-2 to exploit PFD0975w for drug development. In conclusion, our finding will let us to design effective chemotherapy against malaria parasite exploiting PFD0975w as a drug target. 相似文献