全文获取类型
收费全文 | 1216篇 |
免费 | 72篇 |
国内免费 | 1篇 |
专业分类
1289篇 |
出版年
2024年 | 3篇 |
2023年 | 15篇 |
2022年 | 31篇 |
2021年 | 40篇 |
2020年 | 35篇 |
2019年 | 32篇 |
2018年 | 27篇 |
2017年 | 31篇 |
2016年 | 47篇 |
2015年 | 83篇 |
2014年 | 91篇 |
2013年 | 121篇 |
2012年 | 125篇 |
2011年 | 113篇 |
2010年 | 84篇 |
2009年 | 52篇 |
2008年 | 54篇 |
2007年 | 70篇 |
2006年 | 49篇 |
2005年 | 57篇 |
2004年 | 35篇 |
2003年 | 28篇 |
2002年 | 27篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1982年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1966年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有1289条查询结果,搜索用时 15 毫秒
11.
Determinants of Neutralization Resistance in the Envelope Glycoproteins of a Simian-Human Immunodeficiency Virus Passaged In Vivo 下载免费PDF全文
Bijan Etemad-Moghadam Ying Sun Emma K. Nicholson Gunilla B. Karlsson Dominik Schenten Joseph Sodroski 《Journal of virology》1999,73(10):8873-8879
In vivo passage of a simian-human immunodeficiency virus (SHIV-89.6) generated a virus, SHIV-89.6P, that exhibited increased resistance to some neutralizing antibodies (G. B. Karlsson et al., J. Exp. Med. 188:1159-1171, 1998). Here we examine the range of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies to which the passaged virus became resistant and identify envelope glycoprotein determinants of antibody resistance. Compared with the envelope glycoproteins derived from the parental SHIV-89.6, the envelope glycoproteins of the passaged virus were resistant to antibodies directed against the gp120 V3 variable loop and the CD4 binding site. By contrast, both viral envelope glycoproteins were equally sensitive to neutralization by two antibodies, 2G12 and 2F5, that recognize poorly immunogenic structures on gp120 and gp41, respectively. Changes in the V2 and V3 variable loops of gp120 were necessary and sufficient for full resistance to the IgG1b12 antibody, which is directed against the CD4 binding site. Changes in the V3 loop specified complete resistance to a V3 loop-directed antibody, while changes in the V1/V2 loops conferred partial resistance to this antibody. The epitopes of the neutralizing antibodies were not disrupted by the resistance-associated changes. These results indicate that in vivo selection occurs for HIV-1 envelope glycoproteins with variable loop conformations that restrict the access of antibodies to immunogenic neutralization epitopes. 相似文献
12.
A Novel Family of Serine/Threonine Kinases Participating in Spermiogenesis 总被引:5,自引:0,他引:5 下载免费PDF全文
Peter Kueng Zariana Nikolova Valentin Djonov Andrew Hemphill Valeria Rohrbach Dominik Boehlen Gisela Zuercher Anne-Catherine Andres Andrew Ziemiecki 《The Journal of cell biology》1997,139(7):1851-1859
The molecular mechanisms regulating the spectacular cytodifferentiation observed during spermiogenesis are poorly understood. We have recently identified a murine testis-specific serine kinase (tssk) 1, constituting a novel subfamily of serine/threonine kinases. Using low stringency screening we have isolated and molecularly characterized a second closely related family member, tssk 2, which is probably the orthologue of the human DGS-G gene. Expression of tssk 1 and tssk 2 was limited to the testis of sexually mature males. Immunohistochemical staining localized both kinases to the cytoplasm of late spermatids and to structures resembling residual bodies. tssk 1 and tssk 2 were absent in released sperms in the lumen of the seminiferous tubules and the epididymis, demonstrating a tight window of expression restricted to the last stages of spermatid maturation. In vitro kinase assays of immunoprecipitates containing either tssk 1 or tssk 2 revealed no autophosphorylation of the kinases, however, they led to serine phosphorylation of a coprecipitating protein of ~65 kD. A search for interacting proteins using the yeast two-hybrid system with tssk 1 and tssk 2 cDNA as baits and a prey cDNA library from mouse testis, led to the isolation of a novel cDNA, interacting specifically with both tssk 1 and tssk 2, and encoding the coprecipitated 65-kD protein phosphorylated by both kinases. Interestingly, expression of the interacting clone was also testis specific and paralleled the developmental expression observed for the kinases themselves. These results represent the first demonstration of the involvement of a distinct kinase family, the tssk serine/threonine kinases, together with a substrate in the cytodifferentiation of late spermatids to sperms. 相似文献
13.
Dominik P. J. Heib Kerstin Hoedlmoser Peter Anderer Josef Zeitlhofer Georg Gruber Wolfgang Klimesch Manuel Schabus 《PloS one》2013,8(12)
There is growing evidence of the active involvement of sleep in memory consolidation. Besides hippocampal sharp wave-ripple complexes and sleep spindles, slow oscillations appear to play a key role in the process of sleep-associated memory consolidation. Furthermore, slow oscillation amplitude and spectral power increase during the night after learning declarative and procedural memory tasks. However, it is unresolved whether learning-induced changes specifically alter characteristics of individual slow oscillations, such as the slow oscillation up-state length and amplitude, which are believed to be important for neuronal replay. 24 subjects (12 men) aged between 20 and 30 years participated in a randomized, within-subject, multicenter study. Subjects slept on three occasions for a whole night in the sleep laboratory with full polysomnography. Whereas the first night only served for adaptation purposes, the two remaining nights were preceded by a declarative word-pair task or by a non-learning control task. Slow oscillations were detected in non-rapid eye movement sleep over electrode Fz. Results indicate positive correlations between the length of the up-state as well as the amplitude of both slow oscillation phases and changes in memory performance from pre to post sleep. We speculate that the prolonged slow oscillation up-state length might extend the timeframe for the transfer of initial hippocampal to long-term cortical memory representations, whereas the increase in slow oscillation amplitudes possibly reflects changes in the net synaptic strength of cortical networks. 相似文献
14.
High abundance of cockspur (Echinochloa crus-galli) at the geothermal carbon dioxide spring area in Staveinci indicates that this species is able to grow under widely varying CO2 concentrations. Living cockspur plants can even be found very close to gas-releasing vents where growth is significantly reduced. Plant height correlated well with CO2 exposure. The 13C value of the CO2 spring air was –3.9 and 13C values of high-, medium-, and low-CO2 plants were –10.14, –10.44, and –11.95 , respectively. Stomatal response directly followed the prevailing CO2 concentrations, with the highest reduction of stomatal conductance in high CO2 concentration grown plants. Analysis of the curves relating net photosynthetic rate to intercellular CO2 concentration (P
N-Ci curves) revealed higher CO2 compensation concentration in plants growing at higher CO2 concentration. This indicates adjustment of respiration and photosynthetic carbon assimilation according to the prevailing CO2 concentrations during germination and growth. There was no difference in other photosynthetic parameters measured. 相似文献
15.
Martina Bakele Melanie Joos Sofia Burdi Nicolas Allgaier Simone P?schel Birgit Fehrenbacher Martin Schaller Veronica Marcos Jasmin Kümmerle-Deschner Nikolaus Rieber Niels Borregaard Amir Yazdi Andreas Hector Dominik Hartl 《The Journal of biological chemistry》2014,289(8):5320-5329
Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein containing a CARD (ASC), AIM2, and caspase-1. Subcellular fractionation and microscopic analyses further showed that inflammasome components were localized in the cytoplasm and also noncanonically in secretory vesicle and tertiary granule compartments. Whereas IL-1β and IL-18 were expressed at the mRNA level and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1β protein compared with partially purified neutrophils. Serine proteases and caspases were differentially involved in IL-1β release, depending on the stimulus. Spontaneous activation of the NLRP3 inflammasome in neutrophils in vivo affected IL-1β, but not IL-18 release. In summary, these studies show that human neutrophils express key components of the inflammasome machinery in distinct intracellular compartments and release IL-1β and IL-18, but not IL-1α or IL-33 protein. Targeting the neutrophil inflammasome may represent a future therapeutic strategy to modulate neutrophilic inflammatory diseases, such as cystic fibrosis, rheumatoid arthritis, or sepsis. 相似文献
16.
Due to legislative protection, many species, including large carnivores, are currently recolonizing Europe. To address the impending human-wildlife conflicts in advance, predictive habitat models can be used to determine potentially suitable habitat and areas likely to be recolonized. As field data are often limited, quantitative rule based models or the extrapolation of results from other studies are often the techniques of choice. Using the wolf (Canis lupus) in Germany as a model for habitat generalists, we developed a habitat model based on the location and extent of twelve existing wolf home ranges in Eastern Germany, current knowledge on wolf biology, different habitat modeling techniques and various input data to analyze ten different input parameter sets and address the following questions: (1) How do a priori assumptions and different input data or habitat modeling techniques affect the abundance and distribution of potentially suitable wolf habitat and the number of wolf packs in Germany? (2) In a synthesis across input parameter sets, what areas are predicted to be most suitable? (3) Are existing wolf pack home ranges in Eastern Germany consistent with current knowledge on wolf biology and habitat relationships? Our results indicate that depending on which assumptions on habitat relationships are applied in the model and which modeling techniques are chosen, the amount of potentially suitable habitat estimated varies greatly. Depending on a priori assumptions, Germany could accommodate between 154 and 1769 wolf packs. The locations of the existing wolf pack home ranges in Eastern Germany indicate that wolves are able to adapt to areas densely populated by humans, but are limited to areas with low road densities. Our analysis suggests that predictive habitat maps in general, should be interpreted with caution and illustrates the risk for habitat modelers to concentrate on only one selection of habitat factors or modeling technique. 相似文献
17.
18.
David Schäfer Kie Hankins Michelle Allion Ulrike Krewer Franziska Karcher Laurin Derr Rolf Schuster Julia Maibach Stefan Mück Dominik Kramer Reiner Mönig Fabian Jeschull Sven Daboss Tom Philipp Gregor Neusser Jan Romer Krishnaveni Palanisamy Christine Kranz Florian Buchner R. Jürgen Behm Ali Ahmadian Christian Kübel Irshad Mohammad Ago Samoson Raiker Witter Bernd Smarsly Marcus Rohnke 《Liver Transplantation》2024,14(15):2302830
The anode/electrolyte interface behavior, and by extension, the overall cell performance of sodium-ion batteries is determined by a complex interaction of processes that occur at all components of the electrochemical cell across a wide range of size- and timescales. Single-scale studies may provide incomplete insights, as they cannot capture the full picture of this complex and intertwined behavior. Broad, multiscale studies are essential to elucidate these processes. Within this perspectives article, several analytical and theoretical techniques are introduced, and described how they can be combined to provide a more complete and comprehensive understanding of sodium-ion battery (SIB) performance throughout its lifetime, with a special focus on the interfaces of hard carbon anodes. These methods target various length- and time scales, ranging from micro to nano, from cell level to atomistic structures, and account for a broad spectrum of physical and (electro)chemical characteristics. Specifically, how mass spectrometric, microscopic, spectroscopic, electrochemical, thermodynamic, and physical methods can be employed to obtain the various types of information required to understand battery behavior will be explored. Ways are then discussed how these methods can be coupled together in order to elucidate the multiscale phenomena at the anode interface and develop a holistic understanding of their relationship to overall sodium-ion battery function. 相似文献
19.
20.