全文获取类型
收费全文 | 7303篇 |
免费 | 574篇 |
国内免费 | 1篇 |
专业分类
7878篇 |
出版年
2023年 | 57篇 |
2022年 | 107篇 |
2021年 | 222篇 |
2020年 | 141篇 |
2019年 | 153篇 |
2018年 | 172篇 |
2017年 | 152篇 |
2016年 | 252篇 |
2015年 | 421篇 |
2014年 | 445篇 |
2013年 | 527篇 |
2012年 | 675篇 |
2011年 | 635篇 |
2010年 | 391篇 |
2009年 | 359篇 |
2008年 | 499篇 |
2007年 | 424篇 |
2006年 | 413篇 |
2005年 | 351篇 |
2004年 | 310篇 |
2003年 | 245篇 |
2002年 | 260篇 |
2001年 | 47篇 |
2000年 | 42篇 |
1999年 | 50篇 |
1998年 | 43篇 |
1997年 | 36篇 |
1996年 | 32篇 |
1995年 | 34篇 |
1994年 | 28篇 |
1993年 | 17篇 |
1992年 | 39篇 |
1991年 | 29篇 |
1990年 | 21篇 |
1989年 | 27篇 |
1988年 | 14篇 |
1987年 | 18篇 |
1986年 | 21篇 |
1985年 | 19篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 12篇 |
1980年 | 15篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1973年 | 9篇 |
排序方式: 共有7878条查询结果,搜索用时 15 毫秒
91.
Parya Saberi Kristi E. Gamarel Torsten B. Neilands Megan Comfort Nicolas Sheon Lynae A. Darbes Mallory O. Johnson 《PloS one》2012,7(11)
Objective
We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive) male couples'' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple.Design
Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants'' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it.Methods
We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes.Results
Among 328 men (164 couples), 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse.Conclusions
Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact. 相似文献92.
Anirban Ghosh Michelle Davey Ian C. Chute Steven G. Griffiths Scott Lewis Simi Chacko David Barnett Nicolas Crapoulet Sébastien Fournier Andrew Joy Michelle C. Caissie Amanda D. Ferguson Melissa Daigle M. Vicki Meli Stephen M. Lewis Rodney J. Ouellette 《PloS one》2014,9(10)
Recent studies indicate that extracellular vesicles are an important source material for many clinical applications, including minimally-invasive disease diagnosis. However, challenges for rapid and simple extracellular vesicle collection have hindered their application. We have developed and validated a novel class of peptides (which we named venceremin, or Vn) that exhibit nucleotide-independent specific affinity for canonical heat shock proteins. The Vn peptides were validated to specifically and efficiently capture HSP-containing extracellular vesicles from cell culture growth media, plasma, and urine by electron microscopy, atomic force microscopy, sequencing of nucleic acid cargo, proteomic profiling, immunoblotting, and nanoparticle tracking analysis. All of these analyses confirmed the material captured by the Vn peptides was comparable to those purified by the standard ultracentrifugation method. We show that the Vn peptides are a useful tool for the rapid isolation of extracellular vesicles using standard laboratory equipment. Moreover, the Vn peptides are adaptable to diverse platforms and therefore represent an excellent solution to the challenge of extracellular vesicle isolation for research and clinical applications. 相似文献
93.
94.
95.
Souha Berriri Ana Victoria Garcia Nicolas Frei dit Frey Wilfried Rozhon Stéphanie Pateyron Nathalie Leonhardt Jean-Luc Montillet Jeffrey Leung Heribert Hirt Jean Colcombet 《The Plant cell》2012,24(10):4281-4293
Plant mitogen-activated protein kinases (MAPKs) are involved in important processes, including stress signaling and development. In a functional yeast screen, we identified mutations that render Arabidopsis thaliana
MAPKs constitutively active (CA). Importantly, CA-MAPKs maintain their specificity toward known activators and substrates. As a proof-of-concept, Arabidopsis MAPK4 (MPK4) function in plant immunity was investigated. In agreement with the phenotype of mpk4 mutants, CA-MPK4 plants were compromised in pathogen-induced salicylic acid accumulation and disease resistance. MPK4 activity was found to negatively regulate pathogen-associated molecular pattern-induced reactive oxygen species production but had no impact on callose deposition, indicating that CA-MPK4 allows discriminating between processes regulated by MPK4 activity from processes indirectly affected by mpk4 mutation. Finally, MPK4 activity was also found to compromise effector-triggered immunity conditioned by the Toll Interleukin-1 Receptor–nucleotide binding (NB)–Leu-rich repeat (LRR) receptors RPS4 and RPP4 but not by the coiled coil–NB-LRR receptors RPM1 and RPS2. Overall, these data reveal important insights on how MPK4 regulates plant defenses and establishes that CA-MAPKs offer a powerful tool to analyze the function of plant MAPK pathways. 相似文献
96.
Mitochondrial dysfunction in a transgenic mouse model expressing human amyloid precursor protein (APP) with the Arctic mutation 下载免费PDF全文
97.
Isabelle Huvent Amina Kamah François-Xavier Cantrelle Nicolas Barois Christian Slomianny Caroline Smet-Nocca Isabelle Landrieu Guy Lippens 《Biochemical and biophysical research communications》2014
We study the aggregation of a fragment of the neuronal protein Tau that contains part of the proline rich domain and of the microtubule binding repeats. When incubated at 37 °C with heparin, the fragment readily forms fibers as witnessed by Thioflavin T fluorescence. Electron microscopy and NMR spectroscopy show bundled ribbon like structures with most residues rigidly incorporated in the fibril. Without its cysteines, this fragment still forms fibers of a similar morphology, but with lesser Thioflavin T binding sites and more mobility for the C-terminal residues. 相似文献
98.
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
99.
Christophe Habib Armel Houel Aurélie Lunazzi Jean-Fran?ois Bernardet Anne Berit Olsen Hanne Nilsen Alicia E. Toranzo Nuria Castro Pierre Nicolas Eric Duchaud 《Applied and environmental microbiology》2014,80(17):5503-5514
The genus Tenacibaculum, a member of the family Flavobacteriaceae, is an abundant component of marine bacterial ecosystems that also hosts several fish pathogens, some of which are of serious concern for marine aquaculture. Here, we applied multilocus sequence analysis (MLSA) to 114 representatives of most known species in the genus and of the worldwide diversity of the major fish pathogen Tenacibaculum maritimum. Recombination hampers precise phylogenetic reconstruction, but the data indicate intertwined environmental and pathogenic lineages, which suggests that pathogenicity evolved independently in several species. At lower phylogenetic levels recombination is also important, and the species T. maritimum constitutes a cohesive group of isolates. Importantly, the data reveal no trace of long-distance dissemination that could be linked to international fish movements. Instead, the high number of distinct genotypes suggests an endemic distribution of strains. The MLSA scheme and the data described in this study will help in monitoring Tenacibaculum infections in marine aquaculture; we show, for instance, that isolates from tenacibaculosis outbreaks in Norwegian salmon farms are related to T. dicentrarchi, a recently described species. 相似文献
100.
A new photosynthetic, sand‐dwelling marine dinoflagellate, Ailadinium reticulatum gen. et sp. nov., is described from the Jordanian coast in the Gulf of Aqaba, northern Red Sea, based on detailed morphological and molecular data. A. reticulatum is a large (53–61 μm long and 38–48 μm wide), dorsoventrally compressed species, with the epitheca smaller than the hypotheca. The theca of this new species is thick and peculiarly ornamented with round to polygonal depressions forming a foveate‐reticulate thecal surface structure. The Kofoidian thecal tabulation is APC (Po, cp), 4′, 2a, 6′′, 6c, 4s, 6′′′, 1p, 1′′′′ or alternatively it can be interpreted as APC, 4′, 2a, 6′′, 6c, 4s, 6′′′, 2′′′′. The plate pattern of A. reticulatum is noticeably different from described dinoflagellate genera. Phylogenetic analyses based on the SSU and LSU rDNA genes did not show any supported affinities with currently known thecate dinoflagellates. 相似文献