全文获取类型
收费全文 | 5395篇 |
免费 | 436篇 |
国内免费 | 2篇 |
出版年
2023年 | 32篇 |
2022年 | 60篇 |
2021年 | 111篇 |
2020年 | 60篇 |
2019年 | 103篇 |
2018年 | 174篇 |
2017年 | 147篇 |
2016年 | 194篇 |
2015年 | 326篇 |
2014年 | 302篇 |
2013年 | 431篇 |
2012年 | 440篇 |
2011年 | 388篇 |
2010年 | 287篇 |
2009年 | 226篇 |
2008年 | 296篇 |
2007年 | 279篇 |
2006年 | 244篇 |
2005年 | 244篇 |
2004年 | 223篇 |
2003年 | 191篇 |
2002年 | 184篇 |
2001年 | 72篇 |
2000年 | 76篇 |
1999年 | 69篇 |
1998年 | 36篇 |
1997年 | 34篇 |
1996年 | 26篇 |
1995年 | 25篇 |
1994年 | 15篇 |
1992年 | 50篇 |
1991年 | 37篇 |
1990年 | 34篇 |
1989年 | 33篇 |
1988年 | 25篇 |
1987年 | 30篇 |
1986年 | 24篇 |
1985年 | 27篇 |
1984年 | 20篇 |
1983年 | 16篇 |
1982年 | 12篇 |
1980年 | 15篇 |
1979年 | 11篇 |
1975年 | 11篇 |
1974年 | 15篇 |
1973年 | 16篇 |
1972年 | 21篇 |
1970年 | 17篇 |
1968年 | 13篇 |
1965年 | 20篇 |
排序方式: 共有5833条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production
Reginaldo K. Fernandes Tatiana F. Bachiega Daniela R. Rodrigues Marjorie de A. Golim Luciane A. Dias-Melicio Helanderson de A. Balderramas Ramon Kaneno ?ngela M. V. C. Soares 《PloS one》2015,10(3)
Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE2, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE2 inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE2 confirmed an association between PGE2 inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus. 相似文献
5.
Background
With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. 相似文献6.
The cell cycle modulated glycoprotein GP115 is one of the major yeast proteins containing glycosylphosphatidylinositol 总被引:11,自引:0,他引:11
The cell cycle modulated protein gp115 (115 kDa, isoelectric point about 4.8-5) of Saccharomyces cerevisiae undergoes various post-translational modifications. It is N-glycosylated during its maturation along the secretory pathway where an intermediary precursor of 100 kDa (p100), dynamically related to the mature gp115 protein, is detected at the level of endoplasmic reticulum. Moreover, we have shown by the use of metabolic labeling with [35S]methionine, [3H]palmitic acid and myo-[3H]inositol combined with high resolution two-dimensional gel electrophoresis and immunoprecipitation with a specific antiserum, that gp115 is one of the major palmitate- and inositol-containing proteins in yeast. These results, and the susceptibility of gp115 to phosphatidylinositol-specific phospholipase C treatment strongly indicate that gp115 contains the glycosylphosphatidylinositol (GPI) structure as membrane anchor domain. The two-dimensional analysis of the palmitate- and inositol-labeled proteins has also allowed the characterization of other polypeptides which possibly contain a GPI structure. 相似文献
7.
8.
9.
10.