全文获取类型
收费全文 | 366篇 |
免费 | 57篇 |
专业分类
423篇 |
出版年
2022年 | 5篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 11篇 |
2016年 | 12篇 |
2015年 | 11篇 |
2014年 | 21篇 |
2013年 | 19篇 |
2012年 | 24篇 |
2011年 | 20篇 |
2010年 | 12篇 |
2009年 | 11篇 |
2008年 | 19篇 |
2007年 | 32篇 |
2006年 | 20篇 |
2005年 | 19篇 |
2004年 | 27篇 |
2003年 | 26篇 |
2002年 | 17篇 |
2001年 | 5篇 |
2000年 | 13篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1916年 | 1篇 |
排序方式: 共有423条查询结果,搜索用时 9 毫秒
11.
Rapha?l Laurenceau Gérard Péhau-Arnaudet Sonia Baconnais Joseph Gault Christian Malosse Annick Dujeancourt Nathalie Campo Julia Chamot-Rooke Eric Le Cam Jean-Pierre Claverys Rémi Fronzes 《PLoS pathogens》2013,9(6)
Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence. This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria. Transformation requires the binding and internalization of exogenous DNA, the mechanisms of which are unclear. Here, we report the discovery of a transformation pilus at the surface of competent Streptococcus pneumoniae cells. This Type IV-like pilus, which is primarily composed of the ComGC pilin, is required for transformation. We provide evidence that it directly binds DNA and propose that the transformation pilus is the primary DNA receptor on the bacterial cell during transformation in S. pneumoniae. Being a central component of the transformation apparatus, the transformation pilus enables S. pneumoniae, a major Gram-positive human pathogen, to acquire resistance to antibiotics and to escape vaccines through the binding and incorporation of new genetic material. 相似文献
12.
Tu Cam Le Chae-Yoon Yim Songhee Park Nikita Katila Inho Yang Myoung Chong Song Yeo Joon Yoon Dong-Young Choi Hyukjae Choi Sang-Jip Nam William Fenical 《Bioorganic & medicinal chemistry letters》2017,27(14):3123-3126
HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the comparison of NMR data with the lodopyridone A (3). Lodopyridones B and C (1 and 2) possess the thiazole, and chloroquinoline groups which are characteristic features of these molecules. Lodopyridones A–C show weak inhibitory activities on the β-site amyloid precursor protein cleaving enzyme 1 (BACE1). 相似文献
13.
14.
Laura Dyer Pamela Lockyer Yaxu Wu Arnab Saha Chelsea Cyr Martin Moser Xinchun Pi Cam Patterson 《PloS one》2015,10(9)
Formation of the cardiac valves is an essential component of cardiovascular development. Consistent with the role of the bone morphogenetic protein (BMP) signaling pathway in cardiac valve formation, embryos that are deficient for the BMP regulator BMPER (BMP-binding endothelial regulator) display the cardiac valve anomaly mitral valve prolapse. However, how BMPER deficiency leads to this defect is unknown. Based on its expression pattern in the developing cardiac cushions, we hypothesized that BMPER regulates BMP2-mediated signaling, leading to fine-tuned epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. In the BMPER-/- embryo, EMT is dysregulated in the atrioventricular and outflow tract cushions compared with their wild-type counterparts, as indicated by a significant increase of Sox9-positive cells during cushion formation. However, proliferation is not impaired in the developing BMPER-/- valves. In vitro data show that BMPER directly binds BMP2. In cultured endothelial cells, BMPER blocks BMP2-induced Smad activation in a dose-dependent manner. In addition, BMP2 increases the Sox9 protein level, and this increase is inhibited by co-treatment with BMPER. Consistently, in the BMPER-/- embryos, semi-quantitative analysis of Smad activation shows that the canonical BMP pathway is significantly more active in the atrioventricular cushions during EMT. These results indicate that BMPER negatively regulates BMP-induced Smad and Sox9 activity during valve development. Together, these results identify BMPER as a regulator of BMP2-induced cardiac valve development and will contribute to our understanding of valvular defects. 相似文献
15.
16.
The effects of Cry toxins from Bacillus thuringiensis (Berliner) (Bt) on the anthocorid Orius albidipennis Reuter were studied under laboratory conditions. Tritrophic experiments were performed, in which Orius nymphs were fed Helicoverpa armigera (Hübner) larvae reared on a diet with Cry1Ac, Cry1Ab, or Cry2Ab toxins at different concentrations (0, 1, and 10 microg/ml), when supplemented with Ephestia kuehniella Zeller eggs. In complementary experiments, the Bt Cry1Ac toxin was directly fed to Orius nymphs at a very high concentration (1 mg/ml). No effects on prey consumption, developmental time, nymph survival, fecundity, and egg hatching of O. albidipennis were found in either experiment. It can be concluded that the toxins tested do not seem to pose a risk for the anthocorid O. albidipennis, especially when it is exposed through the prey. 相似文献
17.
Younger JM Ren HY Chen L Fan CY Fields A Patterson C Cyr DM 《The Journal of cell biology》2004,167(6):1075-1085
CFTRDeltaF508 exhibits a correctable protein-folding defect that leads to its misfolding and premature degradation, which is the cause of cystic fibrosis (CF). Herein we report on the characterization of the CFTRDeltaF508 biogenic intermediate that is selected for proteasomal degradation and identification of cellular components that polyubiquitinate CFTRDeltaF508. Nonubiquitinated CFTRDeltaF508 accumulates in a kinetically trapped, but folding competent conformation, that is maintained in a soluble state by cytosolic Hsc70. Ubiquitination of Hsc70-bound CFTRDeltaF508 requires CHIP, a U box containing cytosolic cochaperone. CHIP is demonstrated to function as a scaffold that nucleates the formation of a multisubunit E3 ubiquitin ligase whose reconstituted activity toward CFTR is dependent upon Hdj2, Hsc70, and the E2 UbcH5a. Inactivation of the Hsc70-CHIP E3 leads CFTRDeltaF508 to accumulate in a nonaggregated state, which upon lowering of cell growth temperatures, can fold and reach the cell surface. Inhibition of CFTRDeltaF508 ubiquitination can increase its cell surface expression and may provide an approach to treat CF. 相似文献
18.
19.
20.
Hameau L Jeusset J Lafosse S Coulaud D Delain E Unge T Restle T Le Cam E Mirambeau G 《Journal of virology》2001,75(7):3301-3313