首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   265篇
  免费   12篇
  2023年   2篇
  2022年   6篇
  2021年   5篇
  2020年   9篇
  2019年   17篇
  2018年   6篇
  2017年   10篇
  2016年   13篇
  2015年   21篇
  2014年   12篇
  2013年   28篇
  2012年   22篇
  2011年   19篇
  2010年   19篇
  2009年   10篇
  2008年   19篇
  2007年   9篇
  2006年   10篇
  2005年   9篇
  2004年   7篇
  2003年   13篇
  2002年   6篇
  2001年   1篇
  1998年   1篇
  1993年   2篇
  1990年   1篇
排序方式: 共有277条查询结果,搜索用时 15 毫秒
91.
Bacillus subtilis natto is the key microorganism for the industrial production of menaquinone-7. The fermentation of this bacterium in static culture is associated with biofilm formation. The objective of this study was to determine the effect of biofilm formation on menaquinone-7 production to develop a suitable bio-reactor for the production of menaquinone-7. In the static culture, menaquinone-7 biosynthesis showed a linear correlation with biofilm formation (R 2 = 0.67) and cell density (R 2 = 0.7). The amount of biofilm, cell density and menaquinone-7 formation were a function of nutrient and processing conditions. Glycerol, soy peptone, and yeast extract mixture and 40 °C were found to be the optimum nutrients and temperature for accelerating both biofilm and menaquinone-7 biosynthesis in static culture. However, glucose, mixture of soy peptone and yeast extract and 45 °C were found to be the optima for cell density. As compared to the static culture, the biofilm formation was significantly inhibited when a shaken fermentation was used. However, shaking caused only a small decrease on menaquinone-7 production. These results demonstrate that the biofilm formation is not essential for menaquinone-7 biosynthesis. This study underlines the feasibility of using large scale stirred fermentation process for menaquinone-7 production.  相似文献   
92.
Molecular Biology Reports - Evidence has validated the prophylactic effects of exercising on different aspects of health. On the opposite side, immobilization may lead to various destructive...  相似文献   
93.
94.
Vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily. When bound to a variety of vitamin D analogues, VDR manifests a wide diversity of physiological actions. The molecular mechanism by which different vitamin D analogues cause specific responses is not understood. The published crystallographic structures of the ligand binding domain of VDR (VDR-LBD) complexed with ligands that have differential biological activities have exhibited identical protein conformations. Here we report that rat VDR-LBD (rVDR-LBD) in solution exhibits differential chemical shifts when bound to three ligands that cause diverse responses: the natural hormone, 1,25-dihydroxyvitamin D(3) [1,25(OH)?D?], a potent agonist analogue, 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D? [2MD], and an antagonist, 2-methylene-(22E)-(24R)-25-carbobutoxy-26,27-cyclo-22-dehydro-1α,24-dihydroxy-19-norvitamin D? [OU-72]. Ligand-specific chemical shifts mapped not only to residues at or near the binding pocket but also to residues remote from the ligand binding site. The complexes of rVDR-LBD with native hormone and the potent agonist 2MD exhibited chemical shift differences in signals from helix-12, which is part of the AF2 transactivation domain that appears to play a role in the selective recruitment of coactivators. By contrast, formation of the complex of rVDR-LBD with the antagonist OU-72 led to disappearance of signals from residues in helices-11 and -12. We present evidence that disorder in this region of the receptor in the antagonist complex prevents the attachment of coactivators.  相似文献   
95.
96.
Coumarins are the most important class of natural compounds found widely in various plants. Many coumarin derivatives with different biological and pharmacological activities have been synthesized. In this study, the antiapoptotic and cytotoxic effects and DNA‐binding properties of some synthetic coumarin derivatives (4b, 4d, 4f, 4 g (DBP‐g), 4 h and 4j) against K562 cell lines were investigated using different techniques. MTT assay indicated that the DBP‐g compound was more active than other derivatives, with a IC50 value of 55 μM, and therefore this compound was chosen for further investigation. Apoptosis induction was assessed using acridine orange/ethidium bromide double‐staining and cell‐cycle analysis. In addition, in vitro DNA‐binding studies were carried out using ultraviolet–visible light absorption and fluorescence spectroscopy, as well as viscosity measurement and molecular modelling studies. In vitro results indicated that DBP‐g interacted with DNA through a groove‐binding mode with a binding constant (Kb) of 1.17 × 104 M?1. In agreement with other experimental data, molecular docking studies showed that DBP‐g is a minor groove binder. Overall, it can be concluded that DBP‐g could be used as an effective and novel chemotherapeutic agent.  相似文献   
97.
Physiology and Molecular Biology of Plants - The diversity of 11 fatty acid desaturase (fad2) genes has not been investigated between cultivated and wild species in the Carthamus genus. In...  相似文献   
98.
Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection. Previously it has been suggested that CVA24v uses sialic acid-containing glycoconjugates as attachment receptors on corneal cells, but the nature of these receptors is poorly described. Here, we set out to characterize and identify the cellular components serving as receptors for CVA24v. Binding and infection experiments using corneal cells treated with deglycosylating enzymes or metabolic inhibitors of de novo glycosylation suggested that the receptor(s) used by CVA24v are constituted by sialylated O-linked glycans that are linked to one or more cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mock-transfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v. Finally, binding competition experiments using a library of mono- and oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to Neu5Acα2,3Gal disaccharides (Neu5Ac is N-acetylneuraminic acid). These results provide further insights into the early steps of the CVA24v life cycle.  相似文献   
99.
The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer’s disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end-stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end-stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures.  相似文献   
100.
International Journal of Peptide Research and Therapeutics - Our study aims to establish a biocompatible nanostructure for the improved delivery of anticancer peptide, Brevinin-2R, to treat human...  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号