全文获取类型
收费全文 | 1245篇 |
免费 | 89篇 |
出版年
2022年 | 11篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 11篇 |
2018年 | 31篇 |
2017年 | 12篇 |
2016年 | 20篇 |
2015年 | 44篇 |
2014年 | 61篇 |
2013年 | 57篇 |
2012年 | 92篇 |
2011年 | 93篇 |
2010年 | 56篇 |
2009年 | 54篇 |
2008年 | 66篇 |
2007年 | 87篇 |
2006年 | 72篇 |
2005年 | 68篇 |
2004年 | 49篇 |
2003年 | 49篇 |
2002年 | 81篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 6篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 12篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1976年 | 11篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 8篇 |
1969年 | 5篇 |
排序方式: 共有1334条查询结果,搜索用时 883 毫秒
991.
992.
Popper Miroslav Gancarčíková Soňa Maďar Marián Mudroňová Dagmar Hrčková Gabriela Nemcová Radomíra 《Applied microbiology and biotechnology》2016,100(22):9671-9682
Applied Microbiology and Biotechnology - The experiment was carried out on 24 SPF BALB/c female mice and lasted for 15 days with a 5-day antibiotic (ATB) treatment and then... 相似文献
993.
994.
995.
Cyclic AMP (cAMP)is a natural chemoattractant of the social amoeba Dictyostelium discoideum. It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP3), Ca2+ signalling has been shown to have a major role in chemotaxis. Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca2+ concentration by causing the release of Ca2+ from intracellular stores and activating influx of extracellular Ca2+. Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8-9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca2+ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycol-bis(b-aminoethyl)-N,N,N',N'-tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P3 -receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca2+ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented. 相似文献
996.
Wilms' tumor protein Wt1 is an activator of the anti-Müllerian hormone receptor gene Amhr2
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Klattig J Sierig R Kruspe D Besenbeck B Englert C 《Molecular and cellular biology》2007,27(12):4355-4364
The Wilms' tumor protein Wt1 plays an essential role in mammalian urogenital development. WT1 mutations in humans lead to a variety of disorders, including Wilms' tumor, a pediatric kidney cancer, as well as Frasier and Denys-Drash syndromes. Phenotypic anomalies in Denys-Drash syndrome include pseudohermaphroditism and sex reversal in extreme cases. We have used cDNA microarray analyses on Wt1 knockout mice to identify Wt1-dependent genes involved in sexual development. The gene most dramatically affected by Wt1 inactivation was Amhr2, encoding the anti-Müllerian hormone (Amh) receptor 2. Amhr2 is an essential factor for the regression of the Müllerian duct in males, and mutations in AMHR2 lead to the persistent Müllerian duct syndrome, a rare form of male pseudohermaphroditism. Here we show that Wt1 and Amhr2 are coexpressed during urogenital development and that the Wt1 protein binds to the promoter region of the Amhr2 gene. Inactivation and overexpression of Wt1 in cell lines was followed by immediate changes of Amhr2 expression. The identification of Amhr2 as a Wt1 target provides new insights into the role of Wt1 in sexual differentiation and indicates, in addition to its function in early gonad development and sex determination, a novel function for Wt1, namely, in Müllerian duct regression. 相似文献
997.
Ribonuclease P (RNase P) is a ribonucleoprotein enzyme that generates the mature 5' ends of tRNAs. Ubiquitous across all three kingdoms of life, the composition and functional contributions of the RNA and protein components of RNase P differ between the kingdoms. RNA-alone catalytic activity has been reported throughout bacteria, but only for some archaea, and only as trace activity for eukarya. Available information for RNase P from photosynthetic organelles points to large differences to bacterial as well as to eukaryotic RNase P: for spinach chloroplasts, protein-alone activity has been discussed; for RNase P from the cyanelle of the glaucophyte Cyanophora paradoxa, a type of organelle sharing properties of both cyanobacteria and chloroplasts, the proportion of protein was found to be around 80% rather than the usual 10% in bacteria. Furthermore, the latter RNase P was previously found catalytically inactive in the absence of protein under a variety of conditions; however, the RNA could be activated by a cyanobacterial protein, but not by the bacterial RNase P protein from Escherichia coli. Here we demonstrate that, under very high enzyme concentrations, the RNase P RNA from the cyanelle of C. paradoxa displays RNA-alone activity well above the detection level. Moreover, the RNA can be complemented to a functional holoenzyme by the E. coli RNase P protein, further supporting its overall bacterial-like architecture. Mutational analysis and domain swaps revealed that this A,U-rich cyanelle RNase P RNA is globally optimized but conformationally unstable, since changes as little as a single point mutation or a base pair identity switch at positions that are not part of the universally conserved catalytic core led to a complete loss of RNA-alone activity. Likely related to this low robustness, extensive structural changes towards an E. coli-type P5-7/P15-17 subdomain as a canonical interaction site for tRNA 3'-CCA termini could not be coaxed into increased ribozyme activity. 相似文献
998.
999.
Structure and specificity of a quorum-quenching lactonase (AiiB) from Agrobacterium tumefaciens 总被引:1,自引:0,他引:1
N-Acyl-l-homoserine lactone (AHL) mediated quorum-sensing regulates virulence factor production in a variety of Gram-negative bacteria. Proteins capable of degrading these autoinducers have been called "quorum-quenching" enzymes, can block many quorum-sensing dependent phenotypes, and represent potentially useful reagents for clinical, agricultural, and industrial applications. The most characterized quorum-quenching enzymes to date are the AHL lactonases, which are metalloproteins that belong to the metallo-beta-lactamase superfamily. Here, we report the cloning, heterologous expression, purification, metal content, substrate specificity, and three-dimensional structure of AiiB, an AHL lactonase from Agrobacterium tumefaciens. Much like a homologous AHL lactonase from Bacillus thuringiensis, AiiB appears to be a metal-dependent AHL lactonase with broad specificity. A phosphate dianion is bound to the dinuclear zinc site and the active-site structure suggests specific mechanistic roles for an active site tyrosine and aspartate. To our knowledge, this is the second representative structure of an AHL lactonase and the first of an AHL lactonase from a microorganism that also produces AHL autoinducers. This work should help elucidate the hydrolytic ring-opening mechanism of this family of enzymes and also facilitate the design of more effective quorum-quenching catalysts. 相似文献
1000.