全文获取类型
收费全文 | 3675篇 |
免费 | 261篇 |
国内免费 | 1篇 |
专业分类
3937篇 |
出版年
2024年 | 2篇 |
2023年 | 24篇 |
2022年 | 51篇 |
2021年 | 77篇 |
2020年 | 53篇 |
2019年 | 58篇 |
2018年 | 102篇 |
2017年 | 79篇 |
2016年 | 129篇 |
2015年 | 180篇 |
2014年 | 211篇 |
2013年 | 297篇 |
2012年 | 323篇 |
2011年 | 304篇 |
2010年 | 205篇 |
2009年 | 175篇 |
2008年 | 224篇 |
2007年 | 228篇 |
2006年 | 220篇 |
2005年 | 203篇 |
2004年 | 192篇 |
2003年 | 178篇 |
2002年 | 154篇 |
2001年 | 29篇 |
2000年 | 20篇 |
1999年 | 22篇 |
1998年 | 33篇 |
1997年 | 25篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 10篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有3937条查询结果,搜索用时 0 毫秒
61.
62.
63.
Sonia L. Planey 《Molecular membrane biology》2013,30(1-2):14-31
Thio-palmitoylation is the post-translational addition of the 16-carbon fatty acid, palmitate, to the thiol side chain of cysteine residues by a labile thioester bond. Palmitoylation increases the lipophilicity of a protein resulting in dramatic changes in its subcellular distribution such as moving from the endoplasmic reticulum to the plasma membrane or in subtle changes like an increased affinity for cholesterol-rich lipid rafts in membranes. Palmitoylation is also dynamic, making it unique among post-translational protein lipid modifications. Discovering the molecular identity of palmitoyl acyltransferases (PATs) was a watershed event that dramatically accelerated the pace of discovery in the field. Likewise, there has been increased interest in palmitoylation partly because many of the genes encoding PATs have been linked to cancer and other diseases. Now, with a greater understanding of how palmitate is enzymatically attached to proteins, some of the most interesting questions include: What are the substrates of each PAT?; how does a PAT recognize and palmitoylate a substrate?; how are PATs regulated?; and, how is depalmitoylation regulated? The answers to these questions are beginning to unfold due to the recent development of novel assays as well as the expansion and refinement of existing assays. Our ability to understand palmitoylation and its importance to human health and disease is only as good as the methods we use to test our hypotheses. The continued development of methods with increased sensitivity and selectivity is critical to this venture. 相似文献
64.
Anna Marchiani Stefano Mammi Giuliano Siligardi Rohanah Hussain Isabella Tessari Luigi Bubacco Giovanna Delogu Davide Fabbri Maria A. Dettori Daniele Sanna Sonia Dedola Pier A. Serra Paolo Ruzza 《Amino acids》2013,45(2):327-338
Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4–6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy. In addition, the antioxidant properties and the cytoprotective effects in rat pheochromocytoma (PC12) cells prior to intoxication with H2O2, MPP+ and MnCl2 were examined while the Congo red assay was used to evaluate the ability of these compounds to prevent aggregation of AS. We found that the biphenyl zingerone analogue (6) interacts with high affinity with AS and also displays the best antioxidant properties while the biphenyl analogues of dehydrozingerone (4) and of O-methyl-dehydrozingerone (5) are able to partially inhibit the aggregation process of AS, suggesting the potential role of a hydroxylated biphenyl scaffold in the design of AS aggregation inhibitors. 相似文献
65.
Mireille Rack Sonia Valdivia Guido Sonnemann 《The International Journal of Life Cycle Assessment》2013,18(7):1413-1420
Purpose
The paper provides a late report from the United Nations Environment Program (UNEP)/Society of Environmental Toxicology and Chemistry (SETAC) Life Cycle Initiative workshop “Life Cycle Impact Assessment (LCIA)—where we are, trends, and next steps;” it embeds this report into recent development with regard to the envisaged development of global guidance on environmental life cycle impact assessment indicators and related methodologies.Methods
The document is the output of the UNEP/SETAC Life Cycle Initiative’s workshop on “Life Cycle Impact Assessment—where we are, trends, and next steps.” The presentations and discussions held during the workshop reviewed the first two phases of the Life Cycle Initiative and provided an overview of current LCIA activities being conducted by the Initiative, governments and academia, as well as corporate approaches. The outcomes of the workshop are reflected in light of the implementation of the strategy for Phase 3 of the Life Cycle Initiative.Results
The range of views provided during the workshop indicated different user needs, with regards to, amongst other things, the required complexity of the LCIA methodology, associated costs, and the selection of LCIA categories depending on environmental priorities. The workshop’s results signified a number of potential focus areas for Phase 3 of the Initiative, including capacity building efforts concerning LCIA in developing countries and emerging economies, the preparation of training materials on LCIA, the production of global guidance on LCIA, and the potential development of a broader sustainability indicators framework.Conclusions
These suggestions have been taken into account in the strategy for Phase 3 of the Life Cycle Initiative in two flagship projects, one on global capability development on life cycle approaches and the other on global guidance on environmental life cycle impact assessment indicators. In the context of the latter project, first activities are being organized and planned. Moreover, UNEP has included the recommendations in its Rio + 20 Voluntary Commitments: UNEP and SETAC through the UNEP/SETAC Life Cycle Initiative commit to facilitate improved access to good quality life cycle data and databases as well as expanded use of key environmental indicators that allows the measurement and monitoring of progress towards the environmental sustainability of selected product chains. 相似文献66.
Sonia Valdivia Cassia M. L. Ugaya Jutta Hildenbrand Marzia Traverso Bernard Mazijn Guido Sonnemann 《The International Journal of Life Cycle Assessment》2013,18(9):1673-1685
Purpose
To contribute to the upcoming United Nations Conference on Sustainable Development (Rio+20) in 2012 by introducing a life cycle sustainability assessment (LCSA) and showing how it can play a crucial role in moving towards sustainable consumption and production. The publication, titled Towards a Life Cycle Sustainability Assessment, and published by the UNEP/SETAC Life Cycle Initiative aims to show how three life cycle techniques—(environmental) LCA, S-LCA and LCC—can be combined as part of an over-arching LCSA.Methods
The method was demonstrated by evaluating the characteristics of each phase for each life cycle technique. In defining the goal and scope of an LCSA, for example, different aspects should be taken into account to establish the aim of the study as well as the functional unit, system boundaries, impact category and allocation. Then, the data to be collected for the life cycle sustainability inventory can be either in a unit process or on an organisational level. They can also be quantitative or qualitative. Life cycle sustainability impact assessment should consider the relevance of the impacts as well as the perspective of stakeholders. The interpretation should not add up the results, but rather evaluate them jointly. In order to clarify the approach, a case study is presented to evaluate three types of marble according to the proposed method.Results and discussion
The authors have identified that while LCSA is feasible, following areas need more development: data production and acquisition, methodological development, discussion about LCSA criteria (e.g. cutoff rules), definitions and formats of communication and dissemination of LCSA results and the expansion of research and applications combining (environmental) LCA, LCC and S-LCA. The authors also indicate that it is necessary to develop more examples and cases to improve user capacity to analyse the larger picture and therefore address the three dimensions or pillars of sustainability in a systematic way. Software and database providers are called for in order to facilitate user-friendly and accessible tools to promote LCSAs.Conclusions
The application demonstrated that, although methodological improvements are still needed, important steps towards an overarching sustainability assessment have been accomplished. LCSA is possible and should be pursued; however, more efforts should be made to improve the technique and facilitate the studies in order to contribute to a greener economy. 相似文献67.
Luciano Pirone Luigi Vitagliano Sonia Di Gaetano Emilia Pedone 《Journal of molecular recognition : JMR》2013,26(10):488-495
Recent investigations have shown that members of the KCTD family play important roles in fundamental biological processes. Despite their roles, very limited information is available on their structures and molecular organization. By combining different experimental and theoretical techniques, we have here characterized the two folded domains of KCTD12, an integral component and modulator of the GABAB2 receptor. Secondary prediction methods and CD spectroscopy have shown that the N‐terminal domain KCTD12BTB assumes an α/β structure, whereas the C‐terminal domain KCTD12H1 is predominantly characterized by a β‐structure. Binding assays indicate that the two domains independently expressed show a good affinity for each other. This suggests that the overall protein is likely endowed with a rather compact structure with two interacting structured domains joint by a long disordered region. Notably, both KCTD12BTB and KCTD12H1 are tetrameric when individually expressed. This finding could modify the traditional view that ascribes only to POZ/BTB domain a specific oligomerization role. The first quantification of the affinity of KCTD12POZ/BTB for the C‐terminal region of GABAB2 shows that it falls in the low micromolar range. Interestingly, we also demonstrate that a GABAB2‐related peptide is able to bind KCTD12BTB with a very high affinity. This peptide may represent a useful tool for modulating KCTD12/GABAB2 interaction in vitro and may also constitute the starting point for the development of peptidomimetic compounds with a potential for therapeutic applications. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
68.
The regional specialization of brain function has been well documented in the mouse and fruitfly. The expression of regulatory factors in specific regions of the brain during development suggests that they function to establish or maintain this specialization. Here, we focus on two such factors—the Drosophila cephalic gap genes empty spiracles (ems) and orthodenticle (otd), and their vertebrate homologues Emx1/2 and Otx1/2—and review novel insight into their multiple crucial roles in the formation of complex sensory systems. While the early requirement of these genes in specification of the neuroectoderm has been discussed previously, here we consider more recent studies that elucidate the later functions of these genes in sensory system formation in vertebrates and invertebrates. These new studies show that the ems and Emx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective olfactory systems. Moreover, they demonstrate that the otd and Otx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective visual systems. Based on these recent experimental findings, we discuss the possibility that the olfactory and visual systems of flies and mice share a common evolutionary origin, in that the conserved visual and olfactory circuit elements derive from conserved domains of otd/Otx and ems/Emx action in the urbilaterian ancestor. 相似文献
69.
éric Claeyssen Sonia Dorion Audrey Clendenning Jiang Zhou He Owen Wally Jingkui Chen Evgenia L. Auslender Marie-Claude Moisan Mario Jolicoeur Jean Rivoal 《PloS one》2013,8(1)
The metabolism of potato (Solanum tuberosum) roots constitutively over- and underexpressing hexokinase (HK, EC 2.7.1.1) was examined. An 11-fold variation in HK activity resulted in altered root growth, with antisense roots growing better than sense roots. Quantification of sugars, organic acids and amino acids in transgenic roots demonstrated that the manipulation of HK activity had very little effect on the intracellular pools of these metabolites. However, adenylate and free Pi levels were negatively affected by an increase in HK activity. The flux control coefficient of HK over the phosphorylation of glucose was measured for the first time in plants. Its value varied with HK level. It reached 1.71 at or below normal HK activity value and was much lower (0.32) at very high HK levels. Measurements of glycolytic flux and O2 uptake rates demonstrated that the differences in glucose phosphorylation did not affect significantly glycolytic and respiratory metabolism. We hypothesized that these results could be explained by the existence of a futile cycle between the pools of hexose-Ps and carbohydrates. This view is supported by several lines of evidence. Firstly, activities of enzymes capable of catalyzing these reactions were detected in roots, including a hexose-P phosphatase. Secondly, metabolic tracer experiments using 14C-glucose as precursor showed the formation of 14C-fructose and 14C-sucrose. We conclude that futile cycling of hexose-P could be partially responsible for the differences in energetic status in roots with high and low HK activity and possibly cause the observed alterations in growth in transgenic roots. The involvement of HK and futile cycles in the control of glucose-6P metabolism is discussed. 相似文献
70.
Eliane Volchan Isabel A. David Gisella Tavares Billy M. Nascimento Jose M. Oliveira Sonia Gleiser Andre Szklo Cristina Perez Tania Cavalcante Mirtes G. Pereira Leticia Oliveira 《PloS one》2013,8(8)