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   441篇
  免费   59篇
  国内免费   1篇
  2022年   7篇
  2021年   6篇
  2020年   3篇
  2018年   8篇
  2017年   5篇
  2015年   14篇
  2014年   14篇
  2013年   17篇
  2012年   28篇
  2011年   25篇
  2010年   18篇
  2009年   20篇
  2008年   19篇
  2007年   23篇
  2006年   13篇
  2005年   12篇
  2004年   12篇
  2003年   18篇
  2002年   12篇
  2001年   15篇
  2000年   12篇
  1999年   13篇
  1998年   11篇
  1996年   4篇
  1995年   6篇
  1994年   5篇
  1993年   6篇
  1992年   8篇
  1991年   7篇
  1990年   9篇
  1989年   9篇
  1988年   7篇
  1987年   3篇
  1986年   3篇
  1985年   3篇
  1984年   5篇
  1983年   4篇
  1982年   5篇
  1980年   4篇
  1979年   3篇
  1977年   9篇
  1976年   3篇
  1973年   3篇
  1970年   4篇
  1968年   4篇
  1942年   2篇
  1938年   2篇
  1937年   2篇
  1936年   2篇
  1935年   6篇
排序方式: 共有501条查询结果,搜索用时 31 毫秒
41.
42.
Moir  Katherine E.  Ridal  Jeffrey J.  Cumming  Brian F. 《Hydrobiologia》2022,849(6):1417-1436
Hydrobiologia - Throughout the twentieth century, waterfront industries in Cornwall (Ontario, Canada) discharged significant quantities of mercury (Hg) and other industrial effluents to the St....  相似文献   
43.
Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotype with a promising overall profile, exemplified by 19.  相似文献   
44.
Zhang Y  Zhen Y  Dong Y  Xu Z  Yue Y  Golde TE  Tanzi RE  Moir RD  Xie Z 《PloS one》2011,6(11):e27019
Accumulation and deposition of β-amyloid protein (Aβ) are the hallmark features of Alzheimer''s disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase Aβ accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble Aβ oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and Aβ oligomerization in vitro and in vivo. Naïve and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for Aβ; neonatal mice; and conditioned cell culture media containing secreted human Aβ40 or Aβ42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of Aβ. Finally, isoflurane alone induces Aβ42, but not Aβ40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of Aβ42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced Aβ42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients.  相似文献   
45.
The purpose of this study was to examine the influence of recovery duration on various measures of multiple sprint cycling performance. Twenty-five physically active men completed 2 maximal multiple sprint (20 x 5 seconds) cycling tests with contrasting recovery periods (10 or 30 seconds). The mean +/- SD values for age, height, and body mass were 20.6 +/- 1.5 years, 177.2 +/- 5.4 cm, and 78.2 +/- 8.2 kg, respectively. All tests were conducted on a friction-braked cycle ergometer. Longer (30 seconds) recovery periods resulted in significantly (p < 0.05) higher measures of maximum (approximately 4%) and mean (approximately 26%) power output, the former appearing to result from a potentiation effect during the first few sprints. Thirty-second recovery periods also corresponded with significantly lower measures of fatigue (absolute difference: 16.1%; 95% likely range: 14.1-18.2%), heart rate, respiratory exchange ratio, and oxygen uptake. Blood lactate and ratings of perceived exertion (6-20 scale) increased progressively throughout both protocols and were significantly lower with 30-second recovery periods. The results of this study illustrate the considerable influence of recovery duration on various measures of multiple sprint work. Although the precise mechanisms of this response require further investigation, coaches and sport scientists should consider these findings when attempting to develop or evaluate the performance capabilities of athletes involved in multiple sprint sports.  相似文献   
46.
The heme coordination chemistry and spectroscopic properties of Rhodobacter capsulatus cytochrome c' (RCCP) have been compared to data from Alcaligenes xylosoxidans (AXCP), with the aim of understanding the basis for their different reactivities with nitric oxide (NO). Whereas ferrous AXCP reacts with NO to form a predominantly five-coordinate heme-nitrosyl complex via a six-coordinate intermediate, RCCP forms an equilibrium mixture of six-coordinate and five-coordinate heme-nitrosyl species in approximately equal proportions. Ferrous RCCP and AXCP both exhibit high Fe-His stretching frequencies (227 and 231 cm(-)(1), respectively), suggesting that factors other than the Fe-His bond strength account for their differences in heme-nitrosyl coordination number. Resonance Raman spectra of ferrous-nitrosyl RCCP confirm the presence of both five-coordinate and six-coordinate heme-NO complexes. The six-coordinate heme-nitrosyl of RCCP exhibits a fairly typical Fe-NO stretching frequency (569 cm(-)(1)), in contrast to the relatively high value (579 cm(-)(1)) of the AXCP six-coordinate heme-nitrosyl intermediate. It is proposed that NO experiences greater steric hindrance in binding to the distal face of AXCP, as compared to RCCP, leading to a more distorted Fe-N-O geometry and an elevated Fe-NO stretching frequency. Evidence that RCCP has a more accessible distal coordination site than in AXCP stems from the fact that ferric RCCP readily forms a heme complex with exogenous imidazole, whereas AXCP does not. A model is proposed in which distal heme-face accessibility, rather than the proximal Fe-His bond strength, determines the heme-nitrosyl coordination number in cytochromes c'.  相似文献   
47.
How do spores germinate?   总被引:3,自引:0,他引:3  
Spore germination, as defined as those events that result in the loss of the spore-specific properties, is an essentially biophysical process. It occurs without any need for new macromolecular synthesis, so the apparatus required is already present in the mature dormant spore. Germination in response to specific chemical nutrients requires specific receptor proteins, located at the inner membrane of the spore. After penetrating the outer layers of spore coat and cortex, germinant interacts with its receptor: one early consequence of this binding is the movement of monovalent cations from the spore core, followed by Ca2(+) and dipicolinic acid (DPA). In some species, an ion transport protein is also required for these early stages. Early events - including loss of heat resistance, ion movements and partial rehydration of the spore core - can occur without cortex hydrolysis, although the latter is required for complete core rehydration and colony formation from a spore. In Bacillus subtilis two crucial cortex lytic enzymes have been identified: one is CwlJ, which is DPA-responsive and is located at the cortex-coat junction. The second, SleB, is present both in outer layers and at the inner spore membrane, and is more resistant to wet heat than is CwlJ. Cortex hydrolysis leads to the complete rehydration of the spore core, and then enzyme activity within the spore protoplast resumes. We do not yet know what activates SleB activity in the spore, and neither do we have any information at all on how the spore coat is degraded.  相似文献   
48.
We report a system for the efficient removal of a marker flanked by two loxP sites in Streptomyces coelicolor, using a derivative of the temperate phage C31 that expresses Cre recombinase during a transient infection. As the test case for this recombinant phage (called Cre-phage), we present the construction of an in-frame deletion of a gene, pglW, required for phage growth limitation or Pgl in S.coelicolor. Cre-phage was also used for marker deletion in other strains of S.coelicolor.  相似文献   
49.
The exosporium-defective phenotype of a transposon insertion mutant of Bacillus cereus implicated ExsY, a homologue of B. subtilis cysteine-rich spore coat proteins CotY and CotZ, in assembly of an intact exosporium. Single and double mutants of B. cereus lacking ExsY and its paralogue, CotY, were constructed. The exsY mutant spores are not surrounded by an intact exosporium, though they often carry attached exosporium fragments. In contrast, the cotY mutant spores have an intact exosporium, although its overall shape is altered. The single mutants show altered, but different, spore coat properties. The exsY mutant spore coat is permeable to lysozyme, whereas the cotY mutant spores are less resistant to several organic solvents than is the case for the wild type. The exsY cotY double-mutant spores lack exosporium and have very thin coats that are permeable to lysozyme and are sensitive to chloroform, toluene, and phenol. These spore coat as well as exosporium defects suggest that ExsY and CotY are important to correct formation of both the exosporium and the spore coat in B. cereus. Both ExsY and CotY proteins were detected in Western blots of purified wild-type exosporium, in complexes of high molecular weight, and as monomers. Both exsY and cotY genes are expressed at late stages of sporulation.  相似文献   
50.
Rhodobacter capsulatus cytochrome c' (RCCP) has been overexpressed in Escherichia coli, and its spectroscopic and ligand-binding properties have been investigated. It is concluded that the heterologously expressed protein is assembled correctly, as judged by UV-vis absorption, EPR, and resonance Raman (RR) spectroscopy of the unligated protein as well as forms in which the heme is ligated by CO or NO. To probe the oligomerization state of RCCP and its potential influence on heme reactivity, we have compared the properties of wild-type RCCP with a mutant (K42E) that lacks a salt bridge at the subunit interface. Analytical ultracentrifugation indicates that wild-type and K42E proteins are both monomeric in solution, contrary to the homodimeric structure of the crystalline state. Surprisingly, the K42E mutation produces a number of changes at the heme center (nearly 20 A distant), including perturbation of the ferric spin-state equilibrium and a change in the ferrous heme-nitrosyl complex from a six-coordinate/five-coordinate mixture to a predominantly five-coordinate heme-NO species. RR spectra indicate that ferrous K42E and wild-type RCCP both have relatively high Fe-His stretching frequencies, suggesting that the more favored five-coordinate heme-nitrosyl formation in K42E is not caused by a weaker Fe2+-His bond. Nevertheless, the altered reactivity of ferrous K42E with NO, together with its modified ferric spin state, shows that structural changes originating at the dimer interface can affect the properties of the heme center, raising the exciting possibility that intermolecular encounters at the protein surface might modulate the reactivity of cytochrome c' in vivo.  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