全文获取类型
收费全文 | 2273篇 |
免费 | 260篇 |
出版年
2022年 | 16篇 |
2021年 | 26篇 |
2020年 | 21篇 |
2019年 | 19篇 |
2018年 | 30篇 |
2017年 | 27篇 |
2016年 | 64篇 |
2015年 | 107篇 |
2014年 | 105篇 |
2013年 | 123篇 |
2012年 | 151篇 |
2011年 | 144篇 |
2010年 | 114篇 |
2009年 | 60篇 |
2008年 | 107篇 |
2007年 | 114篇 |
2006年 | 113篇 |
2005年 | 86篇 |
2004年 | 101篇 |
2003年 | 71篇 |
2002年 | 70篇 |
2001年 | 54篇 |
2000年 | 79篇 |
1999年 | 60篇 |
1998年 | 26篇 |
1997年 | 19篇 |
1996年 | 19篇 |
1995年 | 13篇 |
1994年 | 15篇 |
1993年 | 26篇 |
1992年 | 31篇 |
1991年 | 33篇 |
1990年 | 35篇 |
1989年 | 25篇 |
1988年 | 25篇 |
1987年 | 19篇 |
1986年 | 19篇 |
1985年 | 19篇 |
1984年 | 24篇 |
1983年 | 25篇 |
1982年 | 18篇 |
1981年 | 18篇 |
1979年 | 16篇 |
1978年 | 14篇 |
1977年 | 20篇 |
1974年 | 17篇 |
1973年 | 21篇 |
1972年 | 16篇 |
1969年 | 21篇 |
1968年 | 12篇 |
排序方式: 共有2533条查询结果,搜索用时 15 毫秒
921.
922.
Ohne Zusammenfassung 相似文献
923.
Uschi Diestel Marcus Resch Kathrin Meinhardt Sigrid Weiler Tina V. Hellmann Thomas D. Mueller Joachim Nickel Jutta Eichler Yves A. Muller 《PloS one》2013,8(6)
The zona pellucida (ZP) domain is present in extracellular proteins such as the zona pellucida proteins and tectorins and participates in the formation of polymeric protein networks. However, the ZP domain also occurs in the cytokine signaling co-receptor transforming growth factor β (TGF-β) receptor type 3 (TGFR-3, also known as betaglycan) where it contributes to cytokine ligand recognition. Currently it is unclear how the ZP domain architecture enables this dual functionality. Here, we identify a novel major TGF-β-binding site in the FG loop of the C-terminal subdomain of the murine TGFR-3 ZP domain (ZP-C) using protein crystallography, limited proteolysis experiments, surface plasmon resonance measurements and synthetic peptides. In the murine 2.7 Å crystal structure that we are presenting here, the FG-loop is disordered, however, well-ordered in a recently reported homologous rat ZP-C structure. Surprisingly, the adjacent external hydrophobic patch (EHP) segment is registered differently in the rat and murine structures suggesting that this segment only loosely associates with the remaining ZP-C fold. Such a flexible and temporarily-modulated association of the EHP segment with the ZP domain has been proposed to control the polymerization of ZP domain-containing proteins. Our findings suggest that this flexibility also extends to the ZP domain of TGFR-3 and might facilitate co-receptor ligand interaction and presentation via the adjacent FG-loop. This hints that a similar C-terminal region of the ZP domain architecture possibly regulates both the polymerization of extracellular matrix proteins and cytokine ligand recognition of TGFR-3. 相似文献
924.
925.
Hsin-Chieh Ma Ying Liu Chunling Wang Michael Strauss Nina Rehage Ying-Han Chen Nihal Altan-Bonnet James Hogle Eckard Wimmer Steffen Mueller Aniko V. Paul Ping Jiang 《PLoS pathogens》2014,10(4)
Glutathione (GSH) is the most abundant cellular thiol playing an essential role in preserving a reduced cellular environment. Cellular GSH levels can be efficiently reduced by the GSH biosynthesis inhibitor, L-buthionine sulfoximine (BSO). The aim of our study was to determine the role of GSH in the growth of two C-cluster enteroviruses, poliovirus type 1 (PV1) and coxsackievirus A20 (CAV20). Our results show that the growth of both PV1 and CAV20 is strongly inhibited by BSO and can be partially reversed by the addition of GSH. BSO has no effect on viral protein synthesis or RNA replication but it strikingly reduces the accumulation of 14S pentamers in infected cells. GSH-pull down assays show that GSH directly interacts with capsid precursors and mature virus made in the absence of BSO whereas capsid precursors produced under GSH-depletion do not bind to GSH. In particular, the loss of binding of GSH may debilitate the stability of 14S pentamers, resulting in their failure to assemble into mature virus. Immunofluorescence cell imaging demonstrated that GSH-depletion did not affect the localization of viral capsid proteins to the replication complex. PV1 BSO resistant (BSOr) mutants evolved readily during passaging of the virus in the presence of BSO. Structural analyses revealed that the BSOr mutations, mapping to VP1 and VP3 capsid proteins, are primarily located at protomer/protomer interfaces. BSOr mutations might, in place of GSH, aid the stability of 14S particles that is required for virion maturation. Our observation that BSOr mutants are more heat resistant and need less GSH than wt virus to be protected from heat inactivation suggests that they possess a more stable capsid. We propose that the role of GSH during enterovirus morphogenesis is to stabilize capsid structures by direct interaction with capsid proteins both during and after the formation of mature virus particles. 相似文献
926.
Dana M. Blumenthal Kevin E. Mueller Julie A. Kray Daniel R. LeCain Elise Pendall Sara Duke T. Jane Zelikova Feike A. Dijkstra David G. Williams Jack A. Morgan 《Ecosystems》2018,21(8):1533-1544
Global changes that alter soil water availability may have profound effects on semiarid ecosystems. Although both elevated CO2 (eCO2) and warming can alter water availability, often in opposite ways, few studies have measured their combined influence on the amount, timing, and temporal variability of soil water. Here, we ask how free air CO2 enrichment (to 600 ppmv) and infrared warming (+?1.5 °C day, +?3 °C night) effects on soil water vary within years and across wet-dry periods in North American mixed-grass prairie. We found that eCO2 and warming interacted to influence soil water and that those interactions varied by season. In the spring, negative effects of warming on soil water largely offset positive effects of eCO2. As the growing season progressed, however, warming reduced soil water primarily (summer) or only (autumn) in plots treated with eCO2. These interactions constrained the combined effect of eCO2 and warming on soil water, which ranged from neutral in spring to positive in autumn. Within seasons, eCO2 increased soil water under drier conditions, and warming decreased soil water under wetter conditions. By increasing soil water under dry conditions, eCO2 also reduced temporal variability in soil water. These temporal patterns explain previously observed plant responses, including reduced leaf area with warming in summer, and delayed senescence with eCO2 plus warming in autumn. They also suggest that eCO2 and warming may favor plant species that grow in autumn, including winter annuals and C3 graminoids, and species able to remain active under the dry conditions moderated by eCO2. 相似文献
927.
T L Vanasek A Khoruts T Zell D L Mueller 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(10):5636-5644
CD4(+) T cells that undergo multiple rounds of cell division during primary Ag challenge in vivo produce IL-2 on secondary Ag rechallenge, whereas cells that fail to progress through the cell cycle are anergic to restimulation. Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. The data suggest that cell cycle progression plays a primary role in the regulation of recall Ag responsiveness in CD4(+) T cells in vivo. CTLA-4 molecules promote clonal anergy development only indirectly by limiting cell cycle progression during the primary response. 相似文献
928.
929.
Gabriel Sigmund Marlene Ågerstrand Alexandre Antonelli Thomas Backhaus Tomas Brodin Miriam L. Diamond Walter R. Erdelen David C. Evers Thilo Hofmann Thorsten Hueffer Adelene Lai Joao P. M. Torres Leonie Mueller Allison L. Perrigo Matthias C. Rillig Andreas Schaeffer Martin Scheringer Kristin Schirmer Ahmed Tlili Anna Soehl Rita Triebskorn Penny Vlahos Colette vom Berg Zhanyun Wang Ksenia J. Groh 《Global Change Biology》2023,29(12):3240-3255
Climate change, biodiversity loss, and chemical pollution are planetary-scale emergencies requiring urgent mitigation actions. As these “triple crises” are deeply interlinked, they need to be tackled in an integrative manner. However, while climate change and biodiversity are often studied together, chemical pollution as a global change factor contributing to worldwide biodiversity loss has received much less attention in biodiversity research so far. Here, we review evidence showing that the multifaceted effects of anthropogenic chemicals in the environment are posing a growing threat to biodiversity and ecosystems. Therefore, failure to account for pollution effects may significantly undermine the success of biodiversity protection efforts. We argue that progress in understanding and counteracting the negative impact of chemical pollution on biodiversity requires collective efforts of scientists from different disciplines, including but not limited to ecology, ecotoxicology, and environmental chemistry. Importantly, recent developments in these fields have now enabled comprehensive studies that could efficiently address the manifold interactions between chemicals and ecosystems. Based on their experience with intricate studies of biodiversity, ecologists are well equipped to embrace the additional challenge of chemical complexity through interdisciplinary collaborations. This offers a unique opportunity to jointly advance a seminal frontier in pollution ecology and facilitate the development of innovative solutions for environmental protection. 相似文献
930.
Keith L. Constantine Mark S. Friedrichs Valentina Goldfarb Philip D. Jeffrey Steven Sheriff Luciano Mueller 《Proteins》1993,15(3):290-311
The dynamic behavior of the polypeptide backbone of a recombinant anti-digoxin antibody VL domain has been characterized by measurements of 15N T1 and T2 relaxation times, 1H–15N NOE values, and 1H–2H exchange rates. These data were acquired with 2D inverse detected heteronuclear 1H–15N NMR methods. The relaxation data are interpreted in terms of model free spectral density functions and exchange contributions to transverse relaxation rates R2 (= 1/T2). All characterized residues display low-amplitude picosecond timescale librational motions. Fifteen residues undergo conformational changes on the nanosecond timescale, and 24 residues have significant R2 exchange contributions, which reflect motions on the microsecond to millisecond timescale. For several residues, microsecond to millisecond motions of nearby aromatic rings are postulated to account for some or all of their observed R2 exchange contributions. The measured 1H–2H exchange rates are correlated with hydrogen bonding patterns and distances from the solvent accessible surface. The degree of local flexibility indicated by the NMR measurements is compared to crystallographic B-factors derived from X-ray analyses of the native Fab and the Fab/digoxin complex. In general, both the NMR and X-ray data indicate enhanced flexibility in the turns, hypervariable loops, and portions of β-strands A, B, and G. However, on a residue-specific level, correlations among the various NMR data, and between the NMR and X-ray data, are often absent. This is attributed to the different dynamic processes and environments that influence the various observables. The combined data indicate that certain regions of the VL domain, including the three hypervariable loops, undergo dynamic changes upon VL:VH association and/ or complexation with digoxin. Overall, the 26–10 VL domain exhibits relatively low flexibility on the ps–ns timescale. The possible functional consequences of this result are considered. © 1993 Wiley-Liss, Inc. 相似文献