全文获取类型
收费全文 | 1654篇 |
免费 | 103篇 |
国内免费 | 2篇 |
出版年
2023年 | 5篇 |
2022年 | 12篇 |
2021年 | 19篇 |
2020年 | 6篇 |
2019年 | 11篇 |
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 19篇 |
2015年 | 53篇 |
2014年 | 76篇 |
2013年 | 92篇 |
2012年 | 135篇 |
2011年 | 125篇 |
2010年 | 71篇 |
2009年 | 69篇 |
2008年 | 118篇 |
2007年 | 113篇 |
2006年 | 117篇 |
2005年 | 111篇 |
2004年 | 114篇 |
2003年 | 94篇 |
2002年 | 82篇 |
2001年 | 15篇 |
2000年 | 16篇 |
1999年 | 23篇 |
1998年 | 29篇 |
1997年 | 32篇 |
1996年 | 20篇 |
1995年 | 13篇 |
1994年 | 17篇 |
1993年 | 14篇 |
1992年 | 20篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 7篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 2篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1957年 | 2篇 |
排序方式: 共有1759条查询结果,搜索用时 265 毫秒
111.
112.
Green C Brown G Dafforn TR Reichhart JM Morley T Lomas DA Gubb D 《Development (Cambridge, England)》2003,130(7):1473-1478
Polymerization of members of the serpin superfamily underlies diseases as diverse as cirrhosis, angioedema, thrombosis and dementia. The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin. We show that necrotic mutations that are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo. These necrotic mutations are temperature sensitive, which is in keeping with the temperature-dependent polymerization of serpins in vitro and the role of childhood fevers in exacerbating liver disease in Z alpha-antitrypsin deficiency. In addition, we identify two nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an S>F amino-acid substitution equivalent to that found in Siiyama-variant antitrypsin (nec(S>F.UAS)) fail to complement nec-null mutations and demonstrate a dominant temperature-dependent inactivation of the wild-type nec allele. Taken together, these data establish Drosophila as a powerful system to study serpin polymerization in vivo. 相似文献
113.
A detailed analysis of the periplasmic electron carriers of the photosynthetic bacterium Ectothiorhodospira sp. has been performed. Two low mid-point redox potential electron carriers, cytochrome c′ and cytochrome c, are detected. A high potential iron–sulfur protein is the only high mid-point redox potential electron transfer component
present in the periplasm. Analysis of light-induced absorption changes shows that this high potential iron–sulfur protein
acts in vivo as efficient electron donor to the photo-oxidized high potential heme of the Ectothiorhodospira sp. reaction center.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
114.
115.
G Protein β Subunit–null Mutants Are Impaired in Phagocytosis and Chemotaxis Due to Inappropriate Regulation of the Actin Cytoskeleton 下载免费PDF全文
Barbara Peracino Jane Borleis Tian Jin Monika Westphal Jean-Marc Schwartz Lijun Wu Enrico Bracco Günther Gerisch Peter Devreotes Salvatore Bozzaro 《The Journal of cell biology》1998,141(7):1529-1537
Chemotaxis and phagocytosis are basically similar in cells of the immune system and in Dictyostelium amebae. Deletion of the unique G protein β subunit in D. discoideum impaired phagocytosis but had little effect on fluid-phase endocytosis, cytokinesis, or random motility. Constitutive expression of wild-type β subunit restored phagocytosis and normal development. Chemoattractants released by cells or bacteria trigger typical transient actin polymerization responses in wild-type cells. In β subunit–null cells, and in a series of β subunit point mutants, these responses were impaired to a degree that correlated with the defect in phagocytosis. Image analysis of green fluorescent protein–actin transfected cells showed that β subunit– null cells were defective in reshaping the actin network into a phagocytic cup, and eventually a phagosome, in response to particle attachment. Our results indicate that signaling through heterotrimeric G proteins is required for regulating the actin cytoskeleton during phagocytic uptake, as previously shown for chemotaxis. Inhibitors of phospholipase C and intracellular Ca2+ mobilization inhibited phagocytosis, suggesting the possible involvement of these effectors in the process. 相似文献
116.
Yin-Shan Yang Laurent Guignard André Padilla François Hoh Marie-Paule Strub Marc-Henri Stern Jean-Marc Lhoste Christian Roumestand 《Journal of biomolecular NMR》1998,11(3):337-354
The human oncoprotein p13
MTCP1
is coded by the MTCP1 gene, a gene involved in chromosomal translocations associated with T-cell prolymphocytic leukemia, a rare form of human leukemia with a mature T-cell phenotype. The primary sequence of p13
MTCP1
is highly and only homologous to that of p14
TCL1
, a product coded by the gene TCL1 which is also involved in T-cell prolymphocytic leukemia. These two proteins probably represent the first members of a new family of oncogenic proteins. We present the three-dimensional solution structure of the recombinant p13
MTCP1
determined by homonuclear proton two-dimensional NMR methods at 600 MHz. After proton resonance assignments, a total of 1253 distance restraints and 64 dihedral restraints were collected. The solution structure of p13
MTCP1
is presented as a set of 20 DYANA structures. The rmsd values with respect to the mean structure for the backbone and all heavy atoms for the conformer family are 1.07 ± 0.19 and 1.71 ± 0.17 Å, when the structured core of the protein (residues 11–103) is considered. The solution structure of p13
MTCP1
consists of an orthogonal -barrel, composed of eight antiparallel -strands which present an original arrangement. The two -pleated loops which emerge from this barrel might constitute the interaction surface with a potential molecular partner. 相似文献
117.
Tuberculosis remains the greatest cause of death worldwide because of a single pathogen. Despite its importance, the genetic basis of the pathogenicity of Mycobacterium tuberculosis remains poorly understood, mainly because the most productive investigative approach, molecular genetic analysis, has been severely hampered by a lack of efficient tools. However, significant advances, including the development of methods for inactivating genes and studying their expression with reporter genes, have been recently made. This progress may lead to opportunities for developing new vaccines and antituberculous drugs. The aim of this review is to examine the present state of the art in mycobacterial molecular genetics and pinpoint some expected or promising areas for future research. 相似文献
118.
119.
120.
Olivia Lenoir Magali Jasiek Carole Hénique Léa Guyonnet Bj?rn Hartleben Tillmann Bork Anna Chipont Kathleen Flosseau Imane Bensaada Alain Schmitt Jean-Marc Massé Michèle Souyri Tobias B Huber Pierre-Louis Tharaux 《Autophagy》2015,11(7):1130-1145
The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN. 相似文献