全文获取类型
收费全文 | 293篇 |
免费 | 30篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 23篇 |
2014年 | 16篇 |
2013年 | 21篇 |
2012年 | 30篇 |
2011年 | 26篇 |
2010年 | 13篇 |
2009年 | 12篇 |
2008年 | 15篇 |
2007年 | 17篇 |
2006年 | 23篇 |
2005年 | 10篇 |
2004年 | 13篇 |
2003年 | 10篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有323条查询结果,搜索用时 31 毫秒
51.
52.
Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
53.
R. Leila Reynald Stefaan Sansen C. David Stout Eric F. Johnson 《The Journal of biological chemistry》2012,287(53):44581-44591
To identify the structural features underlying the distinct substrate and inhibitor profiles of P450 2C19 relative to the closely related human enzymes, P450s 2C8 and 2C9, the atomic structure (Protein Data Bank code 4GQS) of cytochrome P450 2C19 complexed with the inhibitor (2-methyl-1-benzofuran-3-yl)-(4-hydroxy-3,5-dimethylphenyl)methanone (Protein Data Bank chemical component 0XV) was determined to 2.87 Å resolution by x-ray crystallography. The conformation of the peptide backbone of P450 2C19 is most similar to that of P450 2C8, but the substrate-binding cavity of P450 2C8 is much larger than that of P450 2C19 due to differences in the amino acid residues that form the substrate-binding cavities of the two enzymes. In contrast, the substrate-binding cavity of P450 2C19 is much more similar in size to that of the structure of the P450 2C9 flurbiprofen complex than to that of a modified P450 2C9 or that of P450 2C8. The cavities of the P450 2C19 0XV complex and the P450 2C9 flurbiprofen complex differ, however, because the helix B-C loops of the two enzymes are dissimilar. These conformational differences reflect the effects of adjacent structural elements that interact with the B-C loops and that differ between the two enzymes. The availability of a structure for 2C19 will facilitate computational approaches for predictions of substrate and inhibitor binding to this enzyme. 相似文献
54.
Koen B. Tanghe Alexis De Tiège Lieven Pauwels Stefaan Blancke Johan Braeckman 《Biology & philosophy》2018,33(3-4):23
Welch (Biol Philos 32(2):263–279, 2017) has recently proposed two possible explanations for why the field of evolutionary biology is plagued by a steady stream of claims that it needs urgent reform. It is either seriously deficient and incapable of incorporating ideas that are new, relevant and plausible or it is not seriously deficient at all but is prone to attracting discontent and to the championing of ideas that are not very relevant, plausible and/or not really new. He argues for the second explanation. This paper presents a twofold critique of his analysis: firstly, the main calls for reform do not concern the field of evolutionary biology in general but rather, or more specifically, the modern evolutionary synthesis. Secondly, and most importantly, these calls are not only inspired by the factors, enumerated by Welch, but are also, and even primarily, motivated by four problematic characteristics of the modern synthesis. This point is illustrated through a short analysis of the latest reform challenge to the modern synthesis, the so-called extended evolutionary synthesis. We conclude with the suggestion that the modern synthesis should be amended, rather than replaced. 相似文献
55.
Michael Dumbacher Tom Van Dooren Katrien Princen Koen De Witte Mélissa Farinelli Sam Lievens Jan Tavernier Wim Dehaen Stefaan Wera Joris Winderickx Sara Allasia Amuri Kilonda Stéphane Spieser Arnaud Marchand Patrick Chaltin Casper C. Hoogenraad Gerard Griffioen 《Molecular neurodegeneration》2018,13(1):50
Background
Neuronal Ca2+ dyshomeostasis and hyperactivity play a central role in Alzheimer’s disease pathology and progression. Amyloid-beta together with non-genetic risk-factors of Alzheimer’s disease contributes to increased Ca2+ influx and aberrant neuronal activity, which accelerates neurodegeneration in a feed-forward fashion. As such, identifying new targets and drugs to modulate excessive Ca2+ signalling and neuronal hyperactivity, without overly suppressing them, has promising therapeutic potential.Methods
Here we show, using biochemical, electrophysiological, imaging, and behavioural tools, that pharmacological modulation of Rap1 signalling by inhibiting its interaction with Pde6δ normalises disease associated Ca2+ aberrations and neuronal activity, conferring neuroprotection in models of Alzheimer’s disease.Results
The newly identified inhibitors of the Rap1-Pde6δ interaction counteract AD phenotypes, by reconfiguring Rap1 signalling underlying synaptic efficacy, Ca2+ influx, and neuronal repolarisation, without adverse effects in-cellulo or in-vivo. Thus, modulation of Rap1 by Pde6δ accommodates key mechanisms underlying neuronal activity, and therefore represents a promising new drug target for early or late intervention in neurodegenerative disorders.Conclusion
Targeting the Pde6δ-Rap1 interaction has promising therapeutic potential for disorders characterised by neuronal hyperactivity, such as Alzheimer’s disease.56.
Stefaan Rossenu Daisy Dewitte Joël Vandekerckhove Christophe Ampe 《The protein journal》1997,16(5):499-503
Phage display is a technique in which a foreign protein or peptide is presented at the surface of a (filamentous) bacteriophage. This system, developed by Smith [(1985), Science 228, 1315–1317], was originally used to create large libraries of antibodies for the purpose of selecting those that strongly bound a particular antigen. More recently it was also employed to present peptides, domains of proteins, or intact proteins at the surface of phages, again to identify high-affinity interactions with ligands. Here we want to illustrate the use of phage display, in combination with PCR saturation mutagenesis, for the study of protein–protein interactions. Rather than selecting for mutants having high affinity, we systematically investigate the binding of every variant with its natural ligand. Via a modified ELISA we can calculate a relative affinity. As a model system we chose to display thymosin β4 on the phage surface in order to study its interaction with actin. 相似文献
57.
58.
A Low Resistance Calcium/Reduced Titania Passivated Contact for High Efficiency Crystalline Silicon Solar Cells
下载免费PDF全文
![点击此处可从《Liver Transplantation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Thomas G. Allen James Bullock Quentin Jeangros Christian Samundsett Yimao Wan Jie Cui Aïcha Hessler‐Wyser Stefaan De Wolf Ali Javey Andres Cuevas 《Liver Transplantation》2017,7(12)
Recent advances in the efficiency of crystalline silicon (c‐Si) solar cells have come through the implementation of passivated contacts that simultaneously reduce recombination and resistive losses within the contact structure. In this contribution, low resistivity passivated contacts are demonstrated based on reduced titania (TiOx) contacted with the low work function metal, calcium (Ca). By using Ca as the overlying metal in the contact structure we are able to achieve a reduction in the contact resistivity of TiOx passivated contacts of up to two orders of magnitude compared to previously reported data on Al/TiOx contacts, allowing for the application of the Ca/TiOx contact to n‐type c‐Si solar cells with partial rear contacts. Implementing this contact structure on the cell level results in a power conversion efficiency of 21.8% where the Ca/TiOx contact comprises only ≈6% of the rear surface of the solar cell, an increase of 1.5% absolute compared to a similar device fabricated without the TiOx interlayer. 相似文献
59.
The timing of birds' breeding seasons: a review of experiments that manipulated timing of breeding 总被引:1,自引:0,他引:1
Verhulst S Nilsson JA 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1490):399-410
Reproductive success usually declines in the course of the season, which may be a direct effect of breeding time, an effect of quality (individuals with high phenotypic or environmental quality breeding early), or a combination of the two. Being able to distinguish between these possibilities is crucial when trying to understand individual variation in annual routines, for instance when to breed, moult and migrate. We review experiments with free-living birds performed to distinguish between the 'timing' and 'quality' hypothesis. 'Clean' manipulation of breeding time seems impossible, and we therefore discuss strong and weak points of different manipulation techniques. We find that the qualitative results were independent of manipulation technique (inducing replacement clutches versus cross-fostering early and late clutches). Given that the two techniques differ strongly in demands made on the birds, this suggests that potential experimental biases are limited. Overall, the evidence indicated that date and quality are both important, depending on fitness component and species, although evidence for the date hypothesis was found more frequently. We expected both effects to be prevalent, since only if date per se is important, does an incentive exist for high-quality birds to breed early. We discuss mechanisms mediating the seasonal decline in reproductive success, and distinguish between effects of absolute date and relative date, for instance timing relative to seasonal environmental fluctuations or conspecifics. The latter is important at least in some cases, suggesting that the optimal breeding time may be frequency dependent, but this has been little studied. A recurring pattern among cross-fostering studies was that delay experiments provided evidence for the quality hypothesis, while advance experiments provided evidence for the date hypothesis. This indicates that late pairs are constrained from producing a clutch earlier in the season, presumably by the fitness costs this would entail. This provides us with a paradox: evidence for the date hypothesis leads us to conclude that quality is important for the ability to breed early. 相似文献
60.