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81.
The understanding of how proteins evolve to perform novel functions has long been sought by biologists. In this regard, two homologous bacterial enzymes, PafA and Dop, pose an insightful case study, as both rely on similar mechanistic properties, yet catalyze different reactions. PafA conjugates a small protein tag to target proteins, whereas Dop removes the tag by hydrolysis. Given that both enzymes present a similar fold and high sequence similarity, we sought to identify the differences in the amino acid sequence and folding responsible for each distinct activity. We tackled this question using analysis of sequence–function relationships, and identified a set of uniquely conserved residues in each enzyme. Reciprocal mutagenesis of the hydrolase, Dop, completely abolished the native activity, at the same time yielding a catalytically active ligase. Based on the available Dop and PafA crystal structures, this change of activity required a conformational change of a critical loop at the vicinity of the active site. We identified the conserved positions essential for stabilization of the alternative loop conformation, and tracked alternative mutational pathways that lead to a change in activity. Remarkably, all these pathways were combined in the evolution of PafA and Dop, despite their redundant effect on activity. Overall, we identified the residues and structural elements in PafA and Dop responsible for their activity differences. This analysis delineated, in molecular terms, the changes required for the emergence of a new catalytic function from a preexisting one.  相似文献   
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The movement patterns of three commercially important wrasse (Labridae) species inside a small marine protected area (~ 0.15 km2) on the west coast of Norway were analysed over a period of 21 months. The mean distance between capture and recapture locations varied between 10 and 187 m, and was species and season specific. The extent of movement was not related to body size or sex. These results imply that a network of small strategically located marine protected areas can be used as management tools to protect wrasses from size- and sex-selective fishing mortality.  相似文献   
85.
In light of the tendency to present the arts in an integrated fashion in many education systems worldwide, this article examines the consequences of integration for discrete art forms. In particular, we investigate the advantages of adopting a syntegrated approach to the facilitation of arts in teacher preparation. A specific comparison between the implementation of arts curricula in South Africa and Australia is made. The disjuncture between policy and practice in arts education that has been reported internationally needs constant monitoring. We conclude that the heart of curriculum transfer and transformation lies in the classroom.  相似文献   
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Selective Autophagy: Talking with the UPS   总被引:1,自引:0,他引:1  
Far from now are the days when investigators raced to identify the proteolytic system responsible for the degradation of their favorite protein. Nowadays, it is well accepted that a given protein can be degraded by different systems depending on factors such as cell type, cellular conditions, or functionality of each proteolytic pathway. The realization of this sharing of substrates among pathways has also helped to unveil deeper levels of communication among the different proteolytic systems. Thus, cells often respond to blockage of one degradative mechanism by upregulating any of the other available pathways. In addition, effectors and regulators of one proteolytic system can be degraded by a different proteolytic pathway that exerts, in this way, a regulatory function. In this mini review, we describe the different levels of cross-talk among autophagic pathways and the ubiquitin/proteasome system. We also provide examples of how this proteolytic communication is used for compensatory purposes in different pathological conditions and discuss the possible therapeutic potential of targeting the modulators of the cross-talk among proteolytic pathways.  相似文献   
87.
In arid and semi-arid regions of the world, such as Mongolia, the future of water resources under a warming climate is of particular concern. The influence of increasing temperatures on precipitation is difficult to predict because precipitation trends in coming decades could have a high degree of spatial variability. In this study, we applied a rotated principal component analysis (RPCA) to a network of 20 tree-ring chronologies across central Mongolia from 1790 to 1994 to evaluate spatial hydroclimatic variability and to place recent variability in the context of the past several centuries. The RPCA results indicate that the network consists of four tree-growth anomaly regions, which were found to be relatively stable through time and space. Correlation analyses reveal spatial linkages between the tree-growth anomalies and instrumental data, where annual streamflow variability was strongly associated with tree-growth anomalies from their respective regions from 1959 to 1994 (r = 0.52–0.64, p < 0.05). This study highlights the extent of spatial variability in hydroclimate across central Mongolia and emphasizes the value of using tree-ring networks in locations with limited instrumental records.  相似文献   
88.
Protection against protein oxidation by lipophilic and hydrophilic antioxidants in model systems using bovine serum albumin (BSA) in solution alone, or in an emulsion with linolenic acid methyl ester (LnMe) was found to be strongly dependent on the oxidation initiator. Tocopherol, Trolox, or the carotenoids astaxanthin and canthaxanthin were incubated with BSA or BSA/LnMe and oxidation was initiated either with the water-soluble azo-initiator 2,2′ azo-bis-(2-amidinopropane) hydrochloride (AAPH), or FeCl3 and ascorbate, or the Fenton system using FeCl2/EDTA/H2O2, or with the singlet oxygen generating species anthracene-9,10-dipropionic acid disodium 1,4 endoperoxide (NDPO2).

The results show that all the antioxidants tested were inefficient in the system with FeCl3/ascorbate. However, with the other initiating agents, the hydrophilic antioxidant, Trolox, was the most effective in preventing both protein and lipid oxidation. In contrast the lipophilic antioxidants were ineffective in preventing oxidation of BSA in aqueous solution, but did show some moderate antioxidative activity on protein and lipid in the BSA/LnMe system. Using the singlet oxygen generating system it was also demonstrated that Trolox always provided better protection of the protein than tocopherol and the carotenoids in both the BSA and the BSA/LnMe systems. In conclusion, prevention of protein oxidation using a water-soluble antioxidant has a protective effect on the lipid fraction and this approach deserves further attention in complex biological systems.  相似文献   
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The DNA‐binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/β‐catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, β‐catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced β‐catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/β‐catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis.  相似文献   
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