全文获取类型
收费全文 | 317篇 |
免费 | 20篇 |
国内免费 | 9篇 |
专业分类
346篇 |
出版年
2022年 | 3篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 19篇 |
2014年 | 16篇 |
2013年 | 20篇 |
2012年 | 17篇 |
2011年 | 17篇 |
2010年 | 14篇 |
2009年 | 16篇 |
2008年 | 13篇 |
2007年 | 19篇 |
2006年 | 14篇 |
2005年 | 15篇 |
2004年 | 15篇 |
2003年 | 12篇 |
2002年 | 19篇 |
2001年 | 7篇 |
2000年 | 10篇 |
1999年 | 11篇 |
1998年 | 12篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1994年 | 9篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1955年 | 1篇 |
1954年 | 2篇 |
排序方式: 共有346条查询结果,搜索用时 0 毫秒
61.
62.
63.
Leão-Helder AN Krikken AM Gellissen G van der Klei IJ Veenhuis M Kiel JA 《FEBS letters》2004,577(3):491-495
ATG genes are required for autophagy-related processes that transport proteins/organelles destined for proteolytic degradation to the vacuole. Here, we describe the identification and characterisation of the Hansenula polymorpha ATG21 gene. Its gene product Hp-Atg21p, fused to eGFP, had a dual location in the cytosol and in peri-vacuolar dots. We demonstrate that Hp-Atg21p is essential for two separate modes of peroxisome degradation, namely glucose-induced macropexophagy and nitrogen limitation-induced microautophagy. In atg21 cells subjected to macropexophagy conditions, sequestration of peroxisomes tagged for degradation is initiated but fails to complete. 相似文献
64.
Maomian Fan Shelly Roper McBurnett Carrie J. Andrews Amity M. Allman John G. Bruno Johnathan L. Kiel 《Journal of biomolecular techniques》2008,19(5):311-319
Here we describe a new DNA capture element (DCE) sensing system, based on the quenching and dequenching of a double-stranded aptamer. This system shows very good sensitivity and thermal stability. While quenching, dequenching, and separating the DCE systems made from different aptamers (all selected by SELEX), an alternative method to rapidly select aptamers was developed—the Aptamer Selection Express (ASExp). This process has been used to select aptamers against different types of targets (Bacillus anthracis spores, Bacillus thuringiensis spores, MS-2 bacteriophage, ovalbumin, and botulinum neurotoxin). The DCE systems made from botulinum neurotoxin aptamers selected by ASExp have been investigated. The results of this investigation indicate that ASExp can be used to rapidly select aptamers for the DCE sensing system. 相似文献
65.
Evolutionary conservation of protein interaction properties has been shown to be a valuable indication for functional importance. Here we use homology interface modeling of 10 Ras-effector complexes by selecting ortholog proteins from 12 organisms representing the major eukaryotic branches, except plants. We find that with increasing divergence time the sequence similarity decreases with respect to the human protein, but the affinities and association rate constants are conserved as predicted by the protein design algorithm, FoldX. In parallel we have done computer simulations on a minimal network based on Ras-effector interactions, and our results indicate that in the absence of negative feedback, changes in kinetics that result in similar binding constants have strong consequences on network behavior. This, together with the previous results, suggests an important biological role, not only for equilibrium binding constants but also for kinetics in signaling processes involving Ras-effector interactions. Our findings are important to take into consideration in system biology approaches and simulations of biological networks. 相似文献
66.
67.
Bartoszewska M Kiel JA Bovenberg RA Veenhuis M van der Klei IJ 《Applied and environmental microbiology》2011,77(4):1413-1422
We have investigated the significance of autophagy in the production of the β-lactam antibiotic penicillin (PEN) by the filamentous fungus Penicillium chrysogenum. In this fungus PEN production is compartmentalized in the cytosol and in peroxisomes. We demonstrate that under PEN-producing conditions significant amounts of cytosolic and peroxisomal proteins are degraded via autophagy. Morphological analysis, based on electron and fluorescence microscopy, revealed that this phenomenon might contribute to progressive deterioration of late subapical cells. We show that deletion of the P. chrysogenum ortholog of Saccharomyces cerevisiae serine-threonine kinase atg1 results in impairment of autophagy. In P. chrysogenum atg1 cells, a distinct delay in cell degeneration is observed relative to wild-type cells. This phenomenon is associated with an increase in the enzyme levels of the PEN biosynthetic pathway and enhanced production levels of this antibacterial compound. 相似文献
68.
Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited diseases that result in progressive retinal degeneration, characterized by visual field constriction and night blindness. A total of 103 mutations in rhodopsin are linked to RP to date, and the phenotypes range from severe to asymptomatic. To study the relation between phenotype and rhodopsin stability in disease mutants, we used a structure-based approach. For 12 of the mutants located at the protein-lipid interphase, we used the von Heijne water-membrane transfer scale, and we find that 9 of the mutations could affect membrane insertion. For 91 mutants, we used the protein design algorithm FoldX. The 3 asymptomatic mutations had no significant reduced stability, 2 were unsuitable for FoldX analysis since the structure was incorrect in this region, 63 mutations had a significant change in protein stability (> 1.6 kcal/mol), and 23 mutations had energy change values under the prediction error threshold (< 1.6 kcal/mol). Out of these 23, the disease-causing effect could be explained by the involvement in other functions (e.g., glycosylation motifs, the interface with arrestin and transducin, and the cilia-binding motif) for 19 mutants. The remaining 4 mutants were probably incorrectly associated with RP or have functionalities not discovered yet. For destabilizing mutations where clinical data were available, we found a highly significant correlation between FoldX energy changes and the average age of night blindness and between FoldX energy changes and daytime vision loss onset. Our detailed structural, functional, and energetic analysis provides a complete picture of the rhodopsin mutations and can guide mutation-specific therapies. 相似文献
69.
In the methylotrophic yeast Hansenula polymorpha non-selective autophagy, induced by nitrogen starvation, results in the turnover of cytoplasmic components, including peroxisomes. We show that the uptake of these components occurs by invagination of the vacuolar membrane without their prior sequestration and thus differs from the mechanism described for bakers yeast. A selective mode of autophagy in H. polymorpha, namely glucose-induced peroxisome degradation, involves sequestration of individual peroxisomes tagged for degradation by membrane layers that subsequently fuse with the vacuole where the organelle is digested. H. polymorpha pdd mutants are blocked in selective peroxisome degradation. We observed that pdd1-201 is also impaired in non-selective autophagy, whereas this process still normally functions in pdd2-4. These findings suggest that mechanistically distinct processes as selective and non-selective autophagy involve common but also unique genes. 相似文献
70.
Anthony Stuart Gilchrist Deborah CA Shearman Marianne Frommer Kathryn A Raphael Nandan P Deshpande Marc R Wilkins William B Sherwin John A Sved 《BMC genomics》2014,15(1)