全文获取类型
收费全文 | 1669篇 |
免费 | 101篇 |
国内免费 | 75篇 |
专业分类
1845篇 |
出版年
2024年 | 4篇 |
2023年 | 13篇 |
2022年 | 44篇 |
2021年 | 33篇 |
2020年 | 50篇 |
2019年 | 85篇 |
2018年 | 58篇 |
2017年 | 31篇 |
2016年 | 46篇 |
2015年 | 51篇 |
2014年 | 128篇 |
2013年 | 119篇 |
2012年 | 89篇 |
2011年 | 126篇 |
2010年 | 81篇 |
2009年 | 75篇 |
2008年 | 96篇 |
2007年 | 105篇 |
2006年 | 82篇 |
2005年 | 68篇 |
2004年 | 62篇 |
2003年 | 53篇 |
2002年 | 39篇 |
2001年 | 39篇 |
2000年 | 19篇 |
1999年 | 20篇 |
1998年 | 29篇 |
1997年 | 23篇 |
1996年 | 19篇 |
1995年 | 18篇 |
1994年 | 21篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 16篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 8篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有1845条查询结果,搜索用时 0 毫秒
101.
Liu J Chakraborty C Graham CH Barbin YP Dixon SJ Lala PK 《Experimental cell research》2003,286(1):138-151
The serine protease urokinase-type plasminogen activator (uPA) promotes matrix degradation by many cell types, including the invasive extravillous trophoblast (EVT) of the human placenta. The noncatalytic amino-terminal end of uPA binds to uPA receptors (uPARs) expressed by these cells. A highly polarized expression of uPAR-bound uPA at the migration front of EVT cells in situ suggests a functional role of uPA:uPAR interaction in EVT cell migration. The present study examined whether uPA stimulates EVT cell migration, independent of proteolytic function, and investigated some of the signaling pathways involved. Using in vitro-propagated EVT cells in Transwell migration assays, both uPA and its noncatalytic amino-terminal fragment (ATF) were shown to stimulate migration through multiporous polycarbonate (pore size 8 microm) membranes. A uPAR-blocking antibody inhibited basal and ATF-stimulated migration. Migration was found to be stimulated by hypoxic conditions, which upregulates uPAR expression; this stimulation was abrogated with the uPAR-blocking antibody, indicating the role of endogenous uPA in EVT cell migration. Spectrofluorometric measurement of cytosolic calcium in cells treated with uPA and ATF demonstrated a rapid rise in [Ca2+](i), which was prevented by pretreatment of cells with thapsigargin, indicating a release from intracellular stores. Both basal and ATF-mediated migratory responses were suppressed in the presence of selective pharmacological inhibitors LY294002, U73122, and U0126, implicating the respective roles of phosphatidinylinositol 3-kinase (PI 3-K), phospholipase C (PLC), and MEK1/2 in basal and ATF-stimulated migratory capacity. Taken together, these results demonstrate that uPA:uPAR interaction stimulates EVT cell migration, independent of uPA enzymatic activity, using the mitogen-activated protein kinase pathway and calcium signaling events including the participation of PI 3-K and PLC. These findings are relevant to clinical conditions of aberrant trophoblast migration, including spontaneous abortion, preeclampsia, and choriocarcinoma. 相似文献
102.
NSF and p97/VCP: similar at first, different at last 总被引:4,自引:0,他引:4
N-Ethylmaleimide sensitive factor (NSF) and p97/valosin-containing protein (VCP) are distantly related members of the ATPases associated with a variety of cellular activities (AAA) family of proteins. While both proteins have been implied in cellular morphology changes involving membrane compartments or vesicles, more recent evidence seems to imply that NSF is primarily involved in the soluble NSF attachment receptor (SNARE)-mediated vesicle fusion by disassembling the SNARE complex whereas p97/VCP is primarily involved in the extraction of membrane proteins. These functional differences are now corroborated by major structural differences based on recent crystallographic and cryo-electron microscopy studies. This review discusses these recent findings. 相似文献
103.
Regulation of organelle membrane fusion by Pkc1p 总被引:3,自引:1,他引:2
Membrane fusion relies on complex protein machineries, which act in sequence to catalyze the fusion of bilayers. The fusion of endoplasmic reticulum membranes requires the t-SNARE Ufe1p, and the AAA ATPase p97/Cdc48p. While the mechanisms of membrane fusion events have begun to emerge, little is known about how this fusion process is regulated. We provide first evidence that endoplasmic reticulum membrane fusion in yeast is regulated by the action of protein kinase C. Specifically, Pkc1p kinase activity is needed to protect the fusion machinery from ubiquitin-mediated degradation . 相似文献
104.
105.
We have applied laser UV photo-footprinting to characterise kinetically complexes involving the activator protein FIS, RNA polymerase and the tyrT promoter of Escherichia coli. FIS photo-footprints strongly to three binding sites upstream of the core promoter. The polymerase photo-footprints in the near-consensus -35 hexamer on the non-template strand of DNA in a fashion similar to that of stable complexes involving the lacUV5 promoter. The kinetics of the interactions of polymerase alone with the tyrT promoter differ from those observed previously at the lacUV5 promoter. In the absence of FIS, we observe an upstream polymerase-induced signal at -122 within FIS site III that occurs subsequent to changes in the core promoter region and is strongly dependent on negative supercoiling. These observations support the proposal that the upstream region of the promoter is wrapped around the polymerase. We propose that the wrapped DNA allows the polymerase to overcome, at least in part, the barrier to DNA untwisting imparted by the G+C-rich discriminator. We further suggest that FIS plays a similar role and may facilitate polymerase escape. 相似文献
106.
Esser K Tursun B Ingenhoven M Michaelis G Pratje E 《Journal of molecular biology》2002,323(5):835-843
The yeast protein cytochrome c peroxidase (Ccp1) is nuclearly encoded and imported into the mitochondrial intermembrane space, where it is involved in degradation of reactive oxygen species. It is known, that Ccp1 is synthesised as a precursor with a N-terminal pre-sequence, that is proteolytically removed during transport of the protein. Here we present evidence for a new processing pathway, involving novel signal peptidase activities. The mAAA protease subunits Yta10 (Afg3) and Yta12 (Rca1) were identified both to be essential for the first processing step. In addition, the Pcp1 (Ygr101w) gene product was found to be required for the second processing step, yielding the mature Ccp1 protein. The newly identified Pcp1 protein belongs to the rhomboid-GlpG superfamily of putative intramembrane peptidases. Inactivation of the protease motifs in mAAA and Pcp1 blocks the respective steps of proteolysis. A model of coupled Ccp1 transport and N-terminal processing by the mAAA complex and Pcp1 is discussed. Similar processing mechanisms may exist, because the mAAA subunits and the newly identified Pcp1 protein belong to ubiquitous protein families. 相似文献
107.
108.
109.
110.