全文获取类型
收费全文 | 548篇 |
免费 | 52篇 |
专业分类
600篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 9篇 |
2020年 | 3篇 |
2019年 | 9篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 31篇 |
2014年 | 23篇 |
2013年 | 44篇 |
2012年 | 47篇 |
2011年 | 43篇 |
2010年 | 27篇 |
2009年 | 30篇 |
2008年 | 23篇 |
2007年 | 35篇 |
2006年 | 37篇 |
2005年 | 29篇 |
2004年 | 24篇 |
2003年 | 36篇 |
2002年 | 35篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 15篇 |
1997年 | 8篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1982年 | 1篇 |
排序方式: 共有600条查询结果,搜索用时 0 毫秒
111.
112.
Georgette L. Suidan Daniel Duerschmied Gregory M. Dillon Veronique Vanderhorst Thomas G. Hampton Siu Ling Wong Jaymie R. Voorhees Denisa D. Wagner 《PloS one》2013,8(3)
The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (−/−) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system. 相似文献
113.
Sm-like protein Hfq: location of the ATP-binding site and the effect of ATP on Hfq-- RNA complexes 总被引:1,自引:0,他引:1 下载免费PDF全文
Arluison V Mutyam SK Mura C Marco S Sukhodolets MV 《Protein science : a publication of the Protein Society》2007,16(9):1830-1841
Sm-like proteins are ubiquitous ring-shaped oligomers that exhibit a variety of nucleic acid-binding activities. They have been linked functionally to various cellular events involving RNA, and it is generally believed that their activity is exerted via the passive binding of nucleic acids. Our earlier studies of the Sm-like Escherichia coli protein Hfq provided the first evidence indicating that Hfq is an ATP-binding protein. Using a combination of biochemical and genetic techniques, we have now determined a plausible ATP-binding site in Hfq and tested Hfq's ATP-binding affinity and stoichiometry. The results of RNA footprinting and binding analyses suggest that ATP binding by the Hfq-RNA complex results in its significant destabilization. RNA footprinting indicates deprotection of Hfq-bound RNA tracts in the presence of ATP, suggestive of their release by the protein. The results reported herein broaden the scope of potential in vivo roles for Hfq and other Sm-like proteins. 相似文献
114.
115.
116.
Eiglmeier K Wincker P Cattolico L Anthouard V Holm I Eckenberg R Quesneville H Jaillon O Collins FH Weissenbach J Brey PT Roth CW 《Insect biochemistry and molecular biology》2005,35(8):799-814
The only natural mechanism of malaria transmission in sub-Saharan Africa is the mosquito, generally Anopheles gambiae. Blocking malaria parasite transmission by stopping the development of Plasmodium in the insect vector would provide a useful alternative to the current methods of malaria control. Toward this end, it is important to understand the molecular basis of the malaria parasite refractory phenotype in An. gambiae mosquito strains. We have selected and sequenced six bacterial artificial chromosome (BAC) clones from the Pen-1 region that is the major quantitative trait locus involved in Plasmodium encapsulation. The sequence and the annotation of five overlapping BAC clones plus one adjacent, but not contiguous clone, totaling 585kb of genomic sequence from the centromeric end of the Pen-1 region of the PEST strain were compared to that of the genome sequence of the same strain produced by the whole genome shotgun technique. This project identified 23 putative mosquito genes plus putative copies of the retrotransposable elements BEL12 and TRANSIBN1_AG in the six BAC clones. Nineteen of the predicted genes are most similar to their Drosophila melanogaster homologs while one is more closely related to vertebrate genes. Comparison of these new BAC sequences plus previously published BAC sequences to the cognate region of the assembled genome sequence identified three retrotransposons present in one sequence version but not the other. One of these elements, Indy, has not been previously described. These observations provide evidence for the recent active transposition of these elements and demonstrate the plasticity of the Anopheles genome. The BAC sequences strongly support the public whole genome shotgun assembly and automatic annotation while also demonstrating the benefit of complementary genome sequences and of human curation. Importantly, the data demonstrate the differences in the genome sequence of an individual mosquito compared to that of a hypothetical, average genome sequence generated by whole genome shotgun assembly. 相似文献
117.
Lijiang Ma Yavuz Bayram Heather M. McLaughlin Megan T. Cho Alyson Krokosky Clesson E. Turner Kristin Lindstrom Caleb P. Bupp Katey Mayberry Weiyi Mu Joann Bodurtha Veronique Weinstein Neda Zadeh Wendy Alcaraz Zöe Powis Yunru Shao Daryl A. Scott Andrea M. Lewis Janson J. White Shalani N. Jhangiani Elif Yilmaz Gulec Seema R. Lalani James R. Lupski Kyle Retterer Rhonda E. Schnur Ingrid M. Wentzensen Sherri Bale Wendy K. Chung 《Human genetics》2016,135(12):1399-1409
118.
Farar V Mohr F Legrand M Lamotte d'Incamps B Cendelin J Leroy J Abitbol M Bernard V Baud F Fournet V Houze P Klein J Plaud B Tuma J Zimmermann M Ascher P Hrabovska A Myslivecek J Krejci E 《Journal of neurochemistry》2012,122(5):1065-1080
J. Neurochem. (2012) 122, 1065-1080. ABSTRACT: Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA). The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE- deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete. 相似文献
119.
120.
Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response 总被引:1,自引:0,他引:1
BACKGROUND: Checkpoint signaling pathways are of crucial importance for the maintenance of genomic integrity. Within these pathways, the effector kinase Chk1 plays a central role in mediating cell-cycle arrest in response to DNA damage, and it does so by phosphorylating key cell-cycle regulators. RESULTS: By investigating the subcellular distribution of Chk1 by cell fractionation, we observed that around 20% of it localizes to chromatin during all phases of the cell cycle. Furthermore, we found that in response to DNA damage, Chk1 rapidly dissociates from the chromatin. Significantly, we observed a tight correlation between DNA-damage-induced Chk1 phosphorylation and chromatin dissociation, suggesting that phosphorylated Chk1 does not stably associate with chromatin. Consistent with these events being triggered by active checkpoint signaling, inhibition of the DNA-damage-activated kinases ATR and ATM, or siRNA-mediated downregulation of the DNA-damage mediator proteins Claspin and TopBP1, impaired DNA-damage-induced dissociation of Chk1 from chromatin. Finally, we established that Chk1 phosphorylation occurs at localized sites of DNA damage and that constitutive immobilization of Chk1 on chromatin results in a defective DNA-damage-induced checkpoint arrest. CONCLUSIONS: Chromatin association and dissociation appears to be important for proper Chk1 regulation. We propose that in response to DNA damage, PIKK-dependent checkpoint signaling leads to phosphorylation of chromatin-bound Chk1, resulting in its rapid release from chromatin and facilitating the transmission of DNA-damage signals to downstream targets, thereby promoting efficient cell-cycle arrest. 相似文献