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   1348篇
  免费   125篇
  2023年   6篇
  2022年   14篇
  2021年   35篇
  2020年   29篇
  2019年   29篇
  2018年   54篇
  2017年   34篇
  2016年   37篇
  2015年   84篇
  2014年   68篇
  2013年   90篇
  2012年   117篇
  2011年   88篇
  2010年   62篇
  2009年   62篇
  2008年   93篇
  2007年   74篇
  2006年   79篇
  2005年   56篇
  2004年   41篇
  2003年   47篇
  2002年   51篇
  2001年   14篇
  2000年   13篇
  1999年   15篇
  1998年   13篇
  1997年   12篇
  1996年   12篇
  1995年   8篇
  1994年   8篇
  1993年   7篇
  1992年   11篇
  1991年   7篇
  1990年   14篇
  1989年   4篇
  1988年   6篇
  1987年   5篇
  1986年   3篇
  1985年   9篇
  1984年   6篇
  1983年   3篇
  1982年   5篇
  1981年   4篇
  1979年   5篇
  1978年   6篇
  1977年   5篇
  1973年   2篇
  1972年   3篇
  1968年   4篇
  1964年   3篇
排序方式: 共有1473条查询结果,搜索用时 31 毫秒
141.
142.
143.
144.
Centromere repositioning (CR) is a recently discovered biological phenomenon consisting of the emergence of a new centromere along a chromosome and the inactivation of the old one. After a CR, the primary constriction and the centromeric function are localized in a new position while the order of physical markers on the chromosome remains unchanged. These events profoundly affect chromosomal architecture. Since horses, asses, and zebras, whose evolutionary divergence is relatively recent, show remarkable morphological similarity and capacity to interbreed despite their chromosomes differing considerably, we investigated the role of CR in the karyotype evolution of the genus Equus. Using appropriate panels of BAC clones in FISH experiments, we compared the centromere position and marker order arrangement among orthologous chromosomes of Burchelli's zebra (Equus burchelli), donkey (Equus asinus), and horse (Equus caballus). Surprisingly, at least eight CRs took place during the evolution of this genus. Even more surprisingly, five cases of CR have occurred in the donkey after its divergence from zebra, that is, in a very short evolutionary time (approximately 1 million years).These findings suggest that in some species the CR phenomenon could have played an important role in karyotype shaping, with potential consequences on population dynamics and speciation.  相似文献   
145.
The calcium ionophore ionomycin induces apoptosis-like events in the human embryonic kidney cell line at early times. Plasma membrane blebbing, mitochondrial depolarization, externalization of phosphatidylserine, and nuclear permeability changes can all be observed within 15 min of treatment. However, there is no activation of caspases or chromatin condensation. Expression of a fusion protein containing the enhanced green fluorescent protein (EGFP) and human cytosolic Group IVA phospholipase A(2)alpha (EGFP-cPLA(2)alpha) in these cells prevents ionomycin-induced phosphatidylserine externalization and death. Cells expressing the cPLA(2)alpha mutant D43N, which does not bind calcium, retain their susceptibility to ionomycin-induced cell death. Both nonexpressing and EGFP-D43N-cPLA(2)alpha-expressing human embryonic kidney cells can be spared from ionomycin-induced cell death by pretreating them with exogenous arachidonic acid. Moreover, during calcium overload, mitochondrial depolarization is significantly lower in the EGFP-cPLA(2)alpha-expressing cells than in cells expressing normal amounts of cPLA(2)alpha. These results suggest that early cell death events promoted by an overload of calcium can be prevented by the presence of high levels of arachidonic acid.  相似文献   
146.
In synchronized light-dark cycles, stationary-phase cultures of the budding yeast Candida utilis were able to survive heat treatment at 50 degees C with an apparent circadian-like rhythm related to the onset of light. However, in continuous darkness this pattern did not run freely and was markedly dampened. We discuss these findings in terms of the potential circadian control of heat tolerance, which has been described in the fission yeast Schizosaccharomyces pombe. Our results suggest that the resistance pattern observed in C. utilis is most likely an adaptive response to the light-induced generation of reactive oxygen species rather than the occurrence of a truly endogenous circadian rhythm.  相似文献   
147.
Paracoccidioides brasiliensis components interact with host cells and can influence the pathogenesis of paracoccidioidomycosis (PCM). Among the components released by P. brasiliensis, gp 43 and a heavily glycosylated antigen with MM>160 kDa are the most recognized by serum antibodies from patients with PCM. In order to isolate the high MM glycoconjugate, we carried out affinity chromatography of a crude exoantigen preparation on immobilized jacalin. The bound fraction (JBE, jacalin binding exoantigen) consisted of a major antigen of high MM and frequently of an additional 70-kDa minor protein. This protein, designated paracoccin, exhibited selective binding to immobilized GlcNAc, a property that was used for its purification. The structural data of paracoccin obtained by mass spectrometry of tryptic peptides did not match any known protein. Anti-paracoccin serum localized the lectin on the surface of P. brasiliensis yeasts, especially in the budding regions. Paracoccin was able to interact with laminin in a dose-dependent manner. This interaction was inhibited by GlcNAc, followed by D-glucose and D-mannose, but not by D-galactose, N-acetyl-galactosamine or L-fucose. Interestingly, paracoccin induced both resident and elicited mouse peritoneal cavity macrophages to release high and persistent levels of TNF-alpha in vitro, a fact that was associated with high nitric oxide production in elicited cells. Because binding to laminin can favor yeast adhesion and invasion of host tissues, and overproduction of NO has been associated with suppression of cell immunity, paracoccin is suggested to play an important role in PCM pathogenesis.  相似文献   
148.
Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report.  相似文献   
149.
150.
Clostridium perfringens epsilon-toxin binds to receptors on MDCK cells and forms a heptamer in membranes. The mechanism behind the oligomerization of epsilon-toxin was studied using carboxyfluorescein (CF)-loaded liposomes composed of various phosphatidylcholines (PCs). The toxin caused CF to leak from liposomes in a dose-dependent manner. The toxin-induced leakage of CF, binding of the toxin to liposomes, and formation of a functional oligomer increased as the phase-transition temperature (Tm) of the PC used in the liposomes decreased. Surface plasmon resonance analysis using an HPA sensorchip (BIAcore) also revealed that the binding of the toxin to liposomes increased with a decrease in the Tm of the PC used in liposomes. The oligomer that was formed in 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine ([125I]TID)-treated liposomes was labeled, indicating that it inserts into a hydrophobic region. Furthermore, the rate of epsilon-toxin-induced CF leakage was enhanced by treatment with phosphatidylethanolamine or diacylglycerol, which is known to favor a lamellar-to-inverted hexagonal (L-H) phase transition. We show that membrane fluidity in the liposome plays an important role in the binding of the toxin to liposomes, insertion into the hydrophobic region in the bilayer of liposomes, and the assembly process in the bilayer.  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