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   1167篇
  免费   58篇
  2023年   6篇
  2022年   10篇
  2021年   26篇
  2020年   16篇
  2019年   22篇
  2018年   23篇
  2017年   32篇
  2016年   34篇
  2015年   48篇
  2014年   56篇
  2013年   73篇
  2012年   93篇
  2011年   96篇
  2010年   60篇
  2009年   66篇
  2008年   74篇
  2007年   75篇
  2006年   72篇
  2005年   48篇
  2004年   61篇
  2003年   49篇
  2002年   49篇
  2001年   7篇
  2000年   11篇
  1999年   12篇
  1998年   7篇
  1997年   9篇
  1996年   12篇
  1995年   7篇
  1994年   10篇
  1993年   6篇
  1992年   7篇
  1991年   5篇
  1990年   4篇
  1988年   2篇
  1987年   3篇
  1984年   2篇
  1983年   2篇
  1982年   5篇
  1981年   2篇
  1979年   2篇
  1978年   2篇
  1976年   3篇
  1975年   2篇
  1974年   3篇
  1973年   1篇
  1972年   1篇
  1971年   2篇
  1969年   2篇
  1937年   1篇
排序方式: 共有1225条查询结果,搜索用时 15 毫秒
151.
152.
We report on the first sightings of the invasive Rapa Whelk Rapana venosa in Maldonado Bay (Punta del Este Harbor and Gorriti Island) using in vivo, underwater observations and video surveys. The species was first detected in the Río de la Plata (Uruguay and Argentina) in 1999, and by 2004 it had extended its local distribution to Punta del Este at the eastern boundary of the estuary. Observations performed by SCUBA diving showed that R. venosa is preying on native mussels Mytilus edulis and Brachidontes spp., and that formerly abundant mussel beds are being seriously depleted due to a combination of human extraction, habitat deterioration and predation by the Rapa Whelk.  相似文献   
153.
Inverted meiosis, in which sister chromatids segregate before homologous chromosomes, is a common aberration of conventional meiosis (in which sister chromatids segregate after homologous chromosomes) and is routinely observed in certain species. This raises an evolutionary mystery: what is the adaptive advantage of the more common, conventional order of segregation in meiosis? I use a population genetic model to show that asexual mutants arising from inverted meiosis are relatively immune from the deleterious effects of loss of complementation (heterozygosity), unlike the asexual mutants arising from conventional meiosis, in which loss of complementation can outweigh the two‐fold cost of meiosis. Hence, asexual reproduction can replace sexual reproduction with inverted meiosis, but not with conventional meiosis. The results are in line with analogous considerations on other alternative types of reproduction and support the idea that amphimixis is stable in spite of the two‐fold cost of meiosis because loss of complementation in mutant asexuals outweigh the two‐fold cost.  相似文献   
154.
The monoclonal antibody MOv19 directed to a folate binding protein shows temperature-dependent potentiation of binding of the noncompeting monoclonal antibody MOv18 to the relevant antigen, but the mechanism involved in this phinomenon had remained unclear. Use of chimeric versions of both monoclonal antibodies and the F(ab′)2 and fan fragments of MOv19 revealed an increment in MOv18 binding in all combinations irrespective of the orgin of the Fc portin of the monoclonal antibody. The potentiating effect of bivalent MOv19 fragments on 125l-MOv18 binding was similar to that of the entire monoclonal antibody and occurred at saturating concentrations of both reagents at which monovalent binding prevails. Similarly, the monovalent fragment also induced a significant increase in MOv18 bunding. Howener, the potentiation sccurred only at very high concentrations of antibody fragment. Homologous inhibition was drastically reduced using MOv19 Fab fragment, suggesting a low binding stability of the monovalent reagent. Immunoblotting analysis and binding in the presence of exogenous purified folate binding protein indicated a cross-linking between soluble and cell surface molecules mediated by the bivalent monoclonal antibodies. The extentof the increase in MOv18 binging at O°C with high amounts of exogenous folate binding protein was lower than that obtained at 370C in the absence of added molecule. Release of 125l-MOv18 from the cell surface was significantly higher in the absence of MOv19 than in its presence. Affinity constant values of 125l-MOv18 binding evaluated in the presence of MOv19 or control monoclonal antibody MINT5 were comparable, whereas the number of binding sites per cell detected by 125l-MOv18 was significantly higher in the presence of MOv19 than MINT5. Together, the data suggest that monoclonal antibody MOv19 induces a conformational change of the molecule it binds that increases the number of antigenic sites anvailable for MOv18 binding and, in turn, the binding stability of the latter, MOv19 bivalency also contributes to the MOv18 binding increment by cross-linking released and cell surface–anchored folate binding protein molecules. © Wiley-Liss, Inc.  相似文献   
155.
The three species investigated, the European eel, Anguilla anguilla (L.), the Mediterranean moray, Muraena helena L., and the conger eel, Conger coner (L.), represent three different superfamilies of the suborder Anguilloidei (infradivision Elopomorpha). Their hemoglobin systems show peculiar structural properties, which distinuish them from all other teleost species studied. They present acidic and basic components differing greatly in their isoelectric points; the basic components have the highest isoelectric points detected in teleost hemoglobins. While there is one major basic component, multiplicity is present in the acidic components in Muraena and Conger. The polyeptides of the acidic comonents show the same electrophoretic mobility in 8 M urea. In the three species, the electroploretic mobility with urea-SDS of the hemoglobin polypeptides shows a shorter β polypeptide in the basic components. These features had never been investigated among Elopomorpha, and are likely to be phylogenetically relevant.  相似文献   
156.
Several studies support the idea that the polypeptides belonging to the family of insulin and insulin-like growth factors (IGFs) play an important role in brain development and continue to be produced in discrete areas of the adult brain. In numerous neuronal populations within the olfactory bulb, the cerebral and cerebellar cortex, the hippocampus, some diencephalic and brainstem nuclei, the spinal cord and the retina, specific insulin and IGF receptors, as well as crucial components of the intracellular receptor signaling pathway have been demonstrated. Thus, mature neurons are endowed with the cellular machinery to respond to insulin and IGF stimulation. Studies in vitro and in vivo, using normal and transgenic animals, have led to the hypothesis that, in the adult brain, IGF-I not only acts as a trophic factor, but also as a neuromodulator of some higher brain functions, such as long-term potentiation and depression. Furthermore, a trophic effect on certain neuronal populations becomes clearly evident in the ischemic brain or neurodegenerative disorders. Thus, the analysis of the early intracellular signaling pathway for the insulin/IGF receptor family in the brain is providing us with new intriguing findings on the way the mammalian brain is sculpted and operates.  相似文献   
157.
Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells.  相似文献   
158.
159.
160.
The Notch signaling pathway participates in several cellular functional aspects. This signaling has an important role in targeting both DC maturation and DC-mediated T cell responses. Thus, it is essential to investigate the influence of this signaling pathway in the role played by DCs in the pathogenesis of experimental paracoccidioidomycosis. This disease is a granulomatous and systemic mycosis that mainly affects lung tissue and can spread to any other organ and system. In this study, we demonstrated that bone marrow-derived DCs infected with yeasts from Paracoccidioides brasiliensis strain 18 performed efficiently their maturation after the activation of Notch signaling, with an increase in CD80, CD86, CCR7, and CD40 expression and the release of cytokines such as IL-6 and TNF-α. We observed that the inhibition of the γ-secretase DAPT impaired the proliferation of T cells induced by DC stimulation. In conclusion, our data suggest that Notch signaling contributes effectively to the maturation of DCs and the DC-mediated activation of the T cell response in P. brasiliensis infections.  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