全文获取类型
收费全文 | 1040篇 |
免费 | 91篇 |
出版年
2023年 | 3篇 |
2022年 | 12篇 |
2021年 | 25篇 |
2020年 | 13篇 |
2019年 | 17篇 |
2018年 | 28篇 |
2017年 | 22篇 |
2016年 | 27篇 |
2015年 | 54篇 |
2014年 | 52篇 |
2013年 | 69篇 |
2012年 | 88篇 |
2011年 | 83篇 |
2010年 | 60篇 |
2009年 | 41篇 |
2008年 | 63篇 |
2007年 | 58篇 |
2006年 | 46篇 |
2005年 | 64篇 |
2004年 | 40篇 |
2003年 | 39篇 |
2002年 | 39篇 |
2001年 | 15篇 |
2000年 | 10篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 10篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 10篇 |
1989年 | 14篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1983年 | 5篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1976年 | 5篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1970年 | 4篇 |
1940年 | 2篇 |
1856年 | 2篇 |
1855年 | 3篇 |
排序方式: 共有1131条查询结果,搜索用时 15 毫秒
41.
42.
43.
44.
45.
Effects of heat and drought stress on post‐illumination bursts of volatile organic compounds in isoprene‐emitting and non‐emitting poplar 下载免费PDF全文
Werner Jud Elisa Vanzo Ziru Li Andrea Ghirardo Ina Zimmer Thomas D. Sharkey Armin Hansel Jörg‐Peter Schnitzler 《Plant, cell & environment》2016,39(6):1204-1215
Over the last decades, post‐illumination bursts (PIBs) of isoprene, acetaldehyde and green leaf volatiles (GLVs) following rapid light‐to‐dark transitions have been reported for a variety of different plant species. However, the mechanisms triggering their release still remain unclear. Here we measured PIBs of isoprene‐emitting (IE) and isoprene non‐emitting (NE) grey poplar plants grown under different climate scenarios (ambient control and three scenarios with elevated CO2 concentrations: elevated control, periodic heat and temperature stress, chronic heat and temperature stress, followed by recovery periods). PIBs of isoprene were unaffected by elevated CO2 and heat and drought stress in IE, while they were absent in NE plants. On the other hand, PIBs of acetaldehyde and also GLVs were strongly reduced in stress‐affected plants of all genotypes. After recovery from stress, distinct differences in PIB emissions in both genotypes confirmed different precursor pools for acetaldehyde and GLV emissions. Changes in PIBs of GLVs, almost absent in stressed plants and enhanced after recovery, could be mainly attributed to changes in lipoxygenase activity. Our results indicate that acetaldehyde PIBs, which recovered only partly, derive from a new mechanism in which acetaldehyde is produced from methylerythritol phosphate pathway intermediates, driven by deoxyxylulose phosphate synthase activity. 相似文献
46.
Suyoung Yoon Sung-Eun Kim Jong Hyun Kim Ina Yoon Phuong-Thao Tran Jihyae Ann Changhoon Kim Woong Sub Byun Sangkook Lee Sunghoon Kim Jiyoun Lee Jeewoo Lee 《Bioorganic & medicinal chemistry》2019,27(6):1099-1109
Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small molecules that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogues by extensively modifying three different pharmacophoric regions comprising adenine, ribose and leucine. Several effective compounds were identified by cell-based mTORC1 activation assays and further tested for anticancer activity. The selected compounds mostly exhibited selective cytotoxicity toward five different cancer cell lines, supporting the hypothesis that the LRS-mediated mTORC1 pathway is a promising alternative target to current therapeutic approaches. 相似文献
47.
Kristine von Bargen Mirella Scraba Ina Krmer Maren Ketterer Christian Nehls Sina Krokowski Urska Repnik Michaela Wittlich Anna Maaser Pia Zapka Madeleine Bunge Martin Schlesinger Gitta Huth Annette Klees Philipp Hansen Andreas Jeschke Gerd Bendas Olaf Utermhlen Gareth Griffiths Thomas Gutsmann Jens Wohlmann Albert Haas 《Cellular microbiology》2019,21(1)
Professional phagocytic cells such as macrophages are a central part of innate immune defence. They ingest microorganisms into membrane‐bound compartments (phagosomes), which acidify and eventually fuse with lysosomes, exposing their contents to a microbicidal environment. Gram‐positive Rhodococcus equi can cause pneumonia in young foals and in immunocompromised humans. The possession of a virulence plasmid allows them to subvert host defence mechanisms and to multiply in macrophages. Here, we show that the plasmid‐encoded and secreted virulence‐associated protein A (VapA) participates in exclusion of the proton‐pumping vacuolar‐ATPase complex from phagosomes and causes membrane permeabilisation, thus contributing to a pH‐neutral phagosome lumen. Using fluorescence and electron microscopy, we show that VapA is also transferred from phagosomes to lysosomes where it permeabilises the limiting membranes for small ions such as protons. This permeabilisation process is different from that of known membrane pore formers as revealed by experiments with artificial lipid bilayers. We demonstrate that, at 24 hr of infection, virulent R. equi is contained in a vacuole, which is enriched in lysosome material, yet possesses a pH of 7.2 whereas phagosomes containing a vapA deletion mutant have a pH of 5.8 and those with virulence plasmid‐less sister strains have a pH of 5.2. Experimentally neutralising the macrophage endocytic system allows avirulent R. equi to multiply. This observation is mirrored in the fact that virulent and avirulent R. equi multiply well in extracts of purified lysosomes at pH 7.2 but not at pH 5.1. Together these data indicate that the major function of VapA is to generate a pH‐neutral and hence growth‐promoting intracellular niche. VapA represents a new type of Gram‐positive virulence factor by trafficking from one subcellular compartment to another, affecting membrane permeability, excluding proton‐pumping ATPase, and consequently disarming host defences. 相似文献
48.
Roberto Menzel Samuel Dorey Tanja Maier Ina Pahl Armin Hauk 《Biotechnology progress》2022,38(1):e3214
The biopharmaceutical industry gains enormous flexibility in production processes by using sterilized preassembled single-use devices. Gamma irradiation is an established sterilization technology that may be restricted in the future by the availability of 60Co as irradiation source and irradiation capacities. X-ray technology is considered an alternative type of radiation for sterilizing SU equipment. In the context of extractables and leachables—one concern connected with the use of single-use process equipment—the effect of X-ray irradiation on the extractables profile of the materials needs to be compared to established gamma irradiation to qualify this alternative technology. An approach is presented to obtain robust and comprehensive extractables data for materials used in SU devices after sterilization either using X-ray or gamma irradiation. A careful selection of the test items and the test design allows a one-to-one comparison of data obtained from a combination of orthogonal analytical techniques. The extractables of a modern SU film material and the copolyester Tritan™ are evaluated. The data presented allow a risk evaluation on the safety of this new sterilization modality for biopharmaceutical applications. It is demonstrated that the extractables profile of a polymer is not affected by the type of irradiation used for sterilization. 相似文献
49.
Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers 总被引:2,自引:0,他引:2
Permeability coefficients across monolayers of the human colon carcinoma cell line Caco-2, cultured on permeable supports, are commonly used to predict the absorption of orally administered drugs and other xenobiotics. This protocol describes our method for the cultivation, characterization and determination of permeability coefficients of xenobiotics (which are, typically, drug-like compounds) in the Caco-2 model. A few modifications that have been introduced over the years are incorporated in the protocol. The method can be used to trace the permeability of a test compound in two directions, from the apical to the basolateral side or vice versa, and both passive and active transport processes can be studied. The permeability assay can be completed within one working day, provided that the Caco-2 monolayers have been cultured and differentiated on the permeable supports 3 weeks in advance. 相似文献