全文获取类型
收费全文 | 568篇 |
免费 | 57篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 11篇 |
2016年 | 12篇 |
2015年 | 29篇 |
2014年 | 24篇 |
2013年 | 33篇 |
2012年 | 31篇 |
2011年 | 33篇 |
2010年 | 25篇 |
2009年 | 26篇 |
2008年 | 25篇 |
2007年 | 28篇 |
2006年 | 45篇 |
2005年 | 39篇 |
2004年 | 37篇 |
2003年 | 29篇 |
2002年 | 31篇 |
2001年 | 12篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 16篇 |
1997年 | 6篇 |
1996年 | 1篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 9篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有625条查询结果,搜索用时 203 毫秒
171.
Stolzing A Sethe S Grune T 《Redox report : communications in free radical research》2005,10(4):207-213
One of the microglial cell functions is the removal of modified extracellular proteins in the brain. The connection between protein oxidation, proteolysis, and microglial activation is the topic of this review. The effect of various activation agents on microglial cells with regard to changes in substrate uptake, proteolytic capacity and degradation efficiency of different types of oxidized protein materials is reviewed. It is shown that different activation stimuli initiate substrate-specific modulation for uptake and proteolysis, influencing an array of factors including receptor expression, lysosomal pH, and proteasome subunit composition. Age-related alterations in activation and proteolytic capacity in microglial cells are also discussed. In ageing, proteolytic effectiveness is diminished, while microglial cells are chronically activated and lose the oxidative burst ability, possibly supporting a 'vicious circle' of macrophage-induced neurodegeneration. 相似文献
172.
173.
174.
Just as long-term nitrogen loading of grasslands decreases plant species richness and increases plant biomass, we have found
that nitrogen loading decreases insect species richness and increases insect abundances. We sampled 54 plots that had been
maintained at various rates of nitrogen addition for 14 years. Total insect species richness and effective insect diversity,
as well as herbivore and predator species richness, were significantly, negatively related to the rate of nitrogen addition.
However, there was variation in trophic responses to nitrogen. Detritivore species richness increased as nitrogen addition
increased, and parasitoids showed no response. Insect abundances, measured as the number of insects and insect biovolume (an
estimate of biomass), were significantly, positively related to the rate of nitrogen addition, as were the abundances of herbivores
and detritivores. Parasitoid abundance was negatively related to the rate of nitrogen addition. Changes in the insect community
were correlated with changes in the plant community. As rates of nitrogen addition increased, plant species richness decreased,
plant productivity and plant tissue nitrogen increased, and plant composition shifted from C4 to C3 grass species. Along this gradient, total insect species richness and effective insect diversity were most strongly, positively
correlated with plant species richness. Insect biovolume was negatively correlated with plant species richness. Responses
of individual herbivores varied along the nitrogen gradient, but numbers of 13 of the 18 most abundant herbivores were positively
correlated with their host plant biomass. Although insect communities did not respond as strongly as plant communities, insect
species richness, abundance, and composition were impacted by nitrogen addition. This study demonstrates that long-term nitrogen
loading affects the entire food chain, simplifying both plant and insect communities.
Received: 18 May 1999 / Accepted: 5 January 2000 相似文献
175.
Very-low-density lipoproteins (VLDL) isolated from fresh normolipidemic plasma were able to compete with labeled low-density lipoproteins (LDL) for receptor binding as efficiently as LDL in human skin fibroblasts. However, VLDL from fresh plasma failed to stimulate acyl-CoA: cholesterol acyltransferase (ACAT) (EC 2.3.1.26) activity significantly. When plasma was stored at 4 degrees C for 24-48 h before ultracentrifugation, the VLDL were able to stimulate ACAT activity significantly. Proteolytic and lipolytic enzymes do not appear to play a role in this phenomenon. The increased capacity of VLDL from stored plasma to stimulate ACAT activity appears to be due partly to the increase in the internalization and degradation processes. Both the larger and the smaller VLDL subclasses were able to stimulate ACAT activity in the cells. The actual changes that take place in the VLDL molecule during the storage of plasma are not known. 相似文献
176.
J T Salonen P Puska T E Kottke J Tuomilehto A Nissinen 《BMJ (Clinical research ed.)》1983,286(6381):1857-1860
The trends in mortality from coronary heart disease in the 1970s and the differences in trends between counties within Finland were calculated from official mortality statistics among the population aged 35 to 64 years. During this period coronary mortality declined by a mean of 1.1% for men and 2.3% for women annually in the whole of Finland. A community based cardiovascular control programme was started in 1972 in North Karelia, a county in the east of Finland. The decline in coronary mortality in this county between 1969 and 1979 was 24% in men and 51% in women. The decline in the rest of Finland over the same period was 12% in men and 24% in women. The decline in North Karelia was greater than that in other counties of Finland for both men and women and that difference exceeded random variation, with over 95% likelihood for both sexes. Even with adjustment for rates before 1974 with cross-county multiple regression analyses the difference persisted. Although further studies are needed, the changes in coronary mortality in North Karelia suggest that the preventive programme has been effective. 相似文献
177.
D Brdiczka K Bücheler M Kottke V Adams V K Nalam 《Biochimica et biophysica acta》1990,1018(2-3):234-238
178.
179.
Herrera Abreu MT Hughes WE Mele K Lyons RJ Rickwood D Browne BC Bennett HL Vallotton P Brummer T Daly RJ 《Molecular biology of the cell》2011,22(1):105-116
The docking protein Gab2 is overexpressed in several human malignancies, including breast cancer, and is associated with increased metastatic potential. Here we report that Gab2 overexpression in MCF-10A mammary epithelial cells led to delayed cell spreading, a decrease in stress fibers and mature focal adhesions, and enhanced cell migration. Expression of a Gab2 mutant uncoupled from 14-3-3-mediated negative feedback (Gab2(2xA)) led to a more mesenchymal morphology and acquisition of invasive potential. Expression of either Gab2 or Gab2(2xA) led to decreased activation of RhoA, but only the latter increased levels of Rac-GTP. Expression of constitutively active RhoA in MCF-10A/Gab2 cells restored stress fibers and focal adhesions, indicating that Gab2 signals upstream of RhoA to suppress these structures. Mutation of the two Shp2-binding sites to phenylalanine (Gab2(ΔShp2)) markedly reduced the effects of Gab2 on cellular phenotype and RhoA activation. Expression of Gab2 or Gab2(2xA), but not Gab2(ΔShp2), promoted Vav2 phosphorylation and plasma membrane recruitment of p190A RhoGAP. Knockdown of p190A RhoGAP reversed Gab2-mediated effects on stress fibers and focal adhesions. The identification of a novel pathway downstream of Gab2 involving negative regulation of RhoA by p190A RhoGAP sheds new light on the role of Gab2 in cancer progression. 相似文献
180.
Oberpichler I Pierik AJ Wesslowski J Pokorny R Rosen R Vugman M Zhang F Neubauer O Ron EZ Batschauer A Lamparter T 《PloS one》2011,6(10):e26775
Photolyases and cryptochromes are evolutionarily related flavoproteins with distinct functions. While photolyases can repair UV-induced DNA lesions in a light-dependent manner, cryptochromes regulate growth, development and the circadian clock in plants and animals. Here we report about two photolyase-related proteins, named PhrA and PhrB, found in the phytopathogen Agrobacterium tumefaciens. PhrA belongs to the class III cyclobutane pyrimidine dimer (CPD) photolyases, the sister class of plant cryptochromes, while PhrB belongs to a new class represented in at least 350 bacterial organisms. Both proteins contain flavin adenine dinucleotide (FAD) as a primary catalytic cofactor, which is photoreduceable by blue light. Spectral analysis of PhrA confirmed the presence of 5,10-methenyltetrahydrofolate (MTHF) as antenna cofactor. PhrB comprises also an additional chromophore, absorbing in the short wavelength region but its spectrum is distinct from known antenna cofactors in other photolyases. Homology modeling suggests that PhrB contains an Fe-S cluster as cofactor which was confirmed by elemental analysis and EPR spectroscopy. According to protein sequence alignments the classical tryptophan photoreduction pathway is present in PhrA but absent in PhrB. Although PhrB is clearly distinguished from other photolyases including PhrA it is, like PhrA, required for in vivo photoreactivation. Moreover, PhrA can repair UV-induced DNA lesions in vitro. Thus, A. tumefaciens contains two photolyase homologs of which PhrB represents the first member of the cryptochrome/photolyase family (CPF) that contains an iron-sulfur cluster. 相似文献