全文获取类型
收费全文 | 2698篇 |
免费 | 232篇 |
专业分类
2930篇 |
出版年
2024年 | 7篇 |
2023年 | 15篇 |
2022年 | 57篇 |
2021年 | 94篇 |
2020年 | 51篇 |
2019年 | 70篇 |
2018年 | 83篇 |
2017年 | 51篇 |
2016年 | 110篇 |
2015年 | 159篇 |
2014年 | 179篇 |
2013年 | 199篇 |
2012年 | 269篇 |
2011年 | 242篇 |
2010年 | 134篇 |
2009年 | 115篇 |
2008年 | 136篇 |
2007年 | 136篇 |
2006年 | 97篇 |
2005年 | 113篇 |
2004年 | 106篇 |
2003年 | 70篇 |
2002年 | 59篇 |
2001年 | 21篇 |
2000年 | 20篇 |
1999年 | 16篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 12篇 |
1992年 | 14篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 13篇 |
1988年 | 7篇 |
1987年 | 9篇 |
1986年 | 14篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 13篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1978年 | 15篇 |
1977年 | 12篇 |
1976年 | 7篇 |
1969年 | 7篇 |
1967年 | 10篇 |
1943年 | 6篇 |
排序方式: 共有2930条查询结果,搜索用时 0 毫秒
41.
Hawkins CJ Silke J Verhagen AM Foster R Ekert PG Ashley DM 《Apoptosis : an international journal on programmed cell death》2001,6(5):331-338
We have reconstituted the Apaf-1-activated apoptosis mechanism in Sacchromyces cerevisiae such that the presence of a constitutively active form of Apaf-1 together with both Caspase-9 and Caspase-3 results in yeast death. This system is a good model of the Apaf-1-activated pathway in mammalian cells: MIHA (XIAP/hILP), and to a lesser degree MIHB (c-IAP1/HIAP2) and MIHC (c-IAP-2/HIAP1) can inhibit caspases in this system, and protection by IAPs (inhibitor of apoptosis) can be abrogated by coexpression of the Drosophila pro-apoptotic proteins HID and GRIM or the mammalian protein DIABLO/Smac. Using this system we demonstrate that unlike DIABLO/Smac, other proteins which interact with mammalian IAPs (TAB-1, Zap-1, Traf-1 and Traf-2) do not act to antagonise IAP- mediated caspase inhibition. 相似文献
42.
Ashley J. Russo Alyssa J. Mathiowetz Steven Hong Matthew D. Welch Kenneth G. Campellone 《Molecular biology of the cell》2016,27(6):967-978
Small G-proteins are key regulatory molecules that activate the actin nucleation machinery to drive cytoskeletal rearrangements during plasma membrane remodeling. However, the ability of small G-proteins to interact with nucleation factors on internal membranes to control trafficking processes has not been well characterized. Here we investigated roles for members of the Rho, Arf, and Rab G-protein families in regulating WASP homologue associated with actin, membranes, and microtubules (WHAMM), an activator of Arp2/3 complex–mediated actin nucleation. We found that Rab1 stimulated the formation and elongation of WHAMM-associated membrane tubules in cells. Active Rab1 recruited WHAMM to dynamic tubulovesicular structures in fibroblasts, and an active prenylated version of Rab1 bound directly to an N-terminal domain of WHAMM in vitro. In contrast to other G-protein–nucleation factor interactions, Rab1 binding inhibited WHAMM-mediated actin assembly. This ability of Rab1 to regulate WHAMM and the Arp2/3 complex represents a distinct strategy for membrane remodeling in which a Rab G-protein recruits the actin nucleation machinery but dampens its activity. 相似文献
43.
George Aranjuez Ashley Burtscher Ketki Sawant Pralay Majumder Jocelyn A. McDonald 《Molecular biology of the cell》2016,27(12):1898-1910
Migrating cells need to overcome physical constraints from the local microenvironment to navigate their way through tissues. Cells that move collectively have the additional challenge of negotiating complex environments in vivo while maintaining cohesion of the group as a whole. The mechanisms by which collectives maintain a migratory morphology while resisting physical constraints from the surrounding tissue are poorly understood. Drosophila border cells represent a genetic model of collective migration within a cell-dense tissue. Border cells move as a cohesive group of 6−10 cells, traversing a network of large germ line–derived nurse cells within the ovary. Here we show that the border cell cluster is compact and round throughout their entire migration, a shape that is maintained despite the mechanical pressure imposed by the surrounding nurse cells. Nonmuscle myosin II (Myo-II) activity at the cluster periphery becomes elevated in response to increased constriction by nurse cells. Furthermore, the distinctive border cell collective morphology requires highly dynamic and localized enrichment of Myo-II. Thus, activated Myo-II promotes cortical tension at the outer edge of the migrating border cell cluster to resist compressive forces from nurse cells. We propose that dynamic actomyosin tension at the periphery of collectives facilitates their movement through restrictive tissues. 相似文献
44.
Karen L. Soldano Melanie E. Garrett Heidi L. Cope J. Michael Rusnak Nathen J. Ellis Kaitlyn L. Dunlap Allison E. Ashley‐Koch 《Birth defects research. Part B, Developmental and reproductive toxicology》2013,98(5):365-373
Neural tube defects (NTDs) are caused by improper neural tube closure during the early stages of embryonic development. NTDs are hypothesized to have a complex genetic origin and numerous candidate genes have been proposed. The nitric oxide synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina bifida, and interactions between that single nucleotide polymorphism (SNP) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been observed. To evaluate other genetic variation in the NO pathway in the development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using 3109 Caucasian samples in 745 families, we evaluated association in the overall dataset and within specific phenotypic subsets. Haplotype tagging SNPs in the NOS genes were tested for genetic association with NTD subtypes, both for main effects as well as for the presence of interactions with the MTHFR C677T polymorphism. Nominal main effect associations were found with all subtypes, across all three NOS genes, and interactions were observed between SNPs in all three NOS genes and MTHFR C677T. Unlike the previous report, the most significant associations in our dataset were with cranial subtypes and the AG genotype of rs4795067 in NOS2 (p = 0.0014) and the interaction between the rs9658490 G allele in NOS1 and MTHFR 677TT genotype (p = 0.0014). Our data extend the previous findings by implicating a role for all three NOS genes, independently and through interactions with MTHFR, in risk not only for spina bifida, but all NTD subtypes. 相似文献
45.
46.
47.
Crystal structure of a transcription regulator (TM1602) from Thermotoga maritima at 2.3 A resolution
Weekes D Miller MD Krishna SS McMullan D McPhillips TM Acosta C Canaves JM Elsliger MA Floyd R Grzechnik SK Jaroszewski L Klock HE Koesema E Kovarik JS Kreusch A Morse AT Quijano K Spraggon G van den Bedem H Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2007,67(1):247-252
48.
Wan Yun Ho Jer-Cherng Chang Kenneth Lim Amaury Cazenave-Gassiot Aivi T. Nguyen Juat Chin Foo Sneha Muralidharan Ashley Viera-Ortiz Sarah J.M. Ong Jin Hui Hor Ira Agrawal Shawn Hoon Olubankole Aladesuyi Arogundade Maria J. Rodriguez Su Min Lim Seung Hyun Kim John Ravits Shi-Yan Ng Markus R. Wenk Edward B. Lee Greg Tucker-Kellogg Shuo-Chien Ling 《The Journal of cell biology》2021,220(9)
49.
Nader Morshed William T Ralvenius Alexi Nott L Ashley Watson Felicia H Rodriguez Leyla A Akay Brian A Joughin PingChieh Pao Jay Penney Lauren LaRocque Diego Mastroeni LiHuei Tsai Forest M White 《Molecular systems biology》2020,16(12)
Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration. 相似文献