全文获取类型
收费全文 | 286篇 |
免费 | 42篇 |
专业分类
328篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 12篇 |
2017年 | 6篇 |
2016年 | 16篇 |
2015年 | 33篇 |
2014年 | 27篇 |
2013年 | 19篇 |
2012年 | 14篇 |
2011年 | 24篇 |
2010年 | 17篇 |
2009年 | 16篇 |
2008年 | 14篇 |
2007年 | 14篇 |
2006年 | 8篇 |
2005年 | 7篇 |
2004年 | 7篇 |
2003年 | 6篇 |
2002年 | 12篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 4篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 1篇 |
1980年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1948年 | 1篇 |
排序方式: 共有328条查询结果,搜索用时 15 毫秒
91.
92.
Kvin Hervouet Martin Ferri Maliki Ankavay Claire Montpellier Charline Camuzet Virginie Alexandre Aïcha Dembl Ccile Lecoeur Arnold Thomas Foe Peggy Bouquet David Hot Thibaut Vausselin Jean-Michel Saliou Sophie Salom-Desnoulez Alexandre Vandeputte Laurent Marsollier Priscille Brodin Marlne Dreux Yves Rouill Jean Dubuisson Ccile-Marie Aliouat-Denis Laurence Cocquerel 《PLoS pathogens》2022,18(8)
Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. Hepatitis E is usually asymptomatic and self-limiting but it can become chronic in immunocompromised patients and is associated with increased fulminant hepatic failure and mortality rates in pregnant women. HEV genome encodes three proteins including the ORF2 protein that is the viral capsid protein. Interestingly, HEV produces 3 isoforms of the ORF2 capsid protein which are partitioned in different subcellular compartments and perform distinct functions in the HEV lifecycle. Notably, the infectious ORF2 (ORF2i) protein is the structural component of virions, whereas the genome-free secreted and glycosylated ORF2 proteins likely act as a humoral immune decoy. Here, by using a series of ORF2 capsid protein mutants expressed in the infectious genotype 3 p6 HEV strain as well as chimeras between ORF2 and the CD4 glycoprotein, we demonstrated how an Arginine-Rich Motif (ARM) located in the ORF2 N-terminal region controls the fate and functions of ORF2 isoforms. We showed that the ARM controls ORF2 nuclear translocation likely to promote regulation of host antiviral responses. This motif also regulates the dual topology and functionality of ORF2 signal peptide, leading to the production of either cytosolic infectious ORF2i or reticular non-infectious glycosylated ORF2 forms. It serves as maturation site of glycosylated ORF2 by furin, and promotes ORF2-host cell membrane interactions. The identification of ORF2 ARM as a unique central regulator of the HEV lifecycle uncovers how viruses settle strategies to condense their genetic information and hijack cellular processes. 相似文献
93.
Antony S Marchand C Stephen AG Thibaut L Agama KK Fisher RJ Pommier Y 《Nucleic acids research》2007,35(13):4474-4484
By enzymatically hydrolyzing the terminal phosphodiester bond at the 3′-ends of DNA breaks, tyrosyl-DNA phosphodiesterase (Tdp1) repairs topoisomerase-DNA covalent complexes and processes the DNA ends for DNA repair. To identify novel Tdp1 inhibitors, we developed a high-throughput assay that uses electrochemiluminescent (ECL) substrates. Subsequent to screening of 1981 compounds from the ‘diversity set’ of the NCI-Developmental Therapeutics Program, here we report that furamidine inhibits Tdp1at low micromolar concentrations. Inhibition of Tdp1 by furamidine is effective both with single- and double-stranded substrates but is slightly stronger with the duplex DNA. Surface plasmon resonance studies show that furamidine binds both single- and double-stranded DNA, though more weakly with the single-stranded substrate DNA. Thus, the inhibition of Tdp1 activity could in part be due to the binding of furamidine to DNA. However, the inhibition of Tdp1 by furamidine is independent of the substrate DNA sequence. The kinetics of Tdp1 inhibition by furamidine was influenced by the drug to enzyme ratio and duration of the reaction. Comparison with related dications shows that furamidine inhibits Tdp1 more effectively than berenil, while pentamidine was inactive. Thus, furamidine represents the most potent Tdp1 inhibitor reported to date. 相似文献
94.
Denis Lalo? Thibaut Jombart Anne-Béatrice Dufour Katayoun Moazami-Goudarzi 《遗传、选种与进化》2007,39(5):545-567
Working with weakly congruent markers means that consensus genetic structuring of populations requires methods explicitly devoted to this purpose. The method, which is presented here, belongs to the multivariate analyses. This method consists of different steps. First, single-marker analyses were performed using a version of principal component analysis, which is designed for allelic frequencies (%PCA). Drawing confidence ellipses around the population positions enhances %PCA plots. Second, a multiple co-inertia analysis (MCOA) was performed, which reveals the common features of single-marker analyses, builds a reference structure and makes it possible to compare single-marker structures with this reference through graphical tools. Finally, a typological value is provided for each marker. The typological value measures the efficiency of a marker to structure populations in the same way as other markers. In this study, we evaluate the interest and the efficiency of this method applied to a European and African bovine microsatellite data set. The typological value differs among markers, indicating that some markers are more efficient in displaying a consensus typology than others. Moreover, efficient markers in one collection of populations do not remain efficient in others. The number of markers used in a study is not a sufficient criterion to judge its reliability. "Quantity is not quality". 相似文献
95.
96.
Hendrik Jan Thibaut Hilde M. van der Schaar Kjerstin H. W. Lanke Erik Verbeken Martin Andrews Pieter Leyssen Johan Neyts Frank J. M. van Kuppeveld 《Journal of virology》2014,88(5):3048-3051
Coxsackieviruses require phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) for replication but can bypass this need by an H57Y mutation in protein 3A (3A-H57Y). We show that mutant coxsackievirus is not outcompeted by wild-type virus during 10 passages in vitro. In mice, the mutant virus proved as virulent as wild-type virus, even when mice were treated with a PI4KIIIβ inhibitor. Our data suggest that upon emergence, the 3A-H57Y mutant has the fitness to establish a resistant population with a virulence similar to that of wild-type virus. 相似文献
97.
Bees (Anthophila) are one of the major groups of angiosperm-pollinating insects and accordingly are widely studied in both basic and applied research, for which it is essential to have a clear understanding of their phylogeny, and evolutionary history. Direct evidence of bee evolutionary history has been hindered by a dearth of available fossils needed to determine the timing and tempo of their diversification, as well as episodes of extinction. Here we describe four new compression fossils of bees from three different deposits (Miocene of la Cerdanya, Spain; Oligocene of Céreste, France; and Eocene of the Green River Formation, U.S.A.). We assess the similarity of the forewing shape of the new fossils with extant and fossil taxa using geometric morphometrics analyses. Predictive discriminant analyses show that three fossils share similar forewing shapes with the Apidae [one of uncertain tribal placement and perhaps near Euglossini, one definitive bumble bee (Bombini), and one digger bee (Anthophorini)], while one fossil is more similar to the Andrenidae. The corbiculate fossils are described as Euglossopteryx biesmeijeri De Meulemeester, Michez, & Engel, gen. nov. sp. nov. (type species of Euglossopteryx Dehon & Engel, n. gen.) and Bombus cerdanyensis Dehon, De Meulemeester, & Engel, sp. nov. They provide new information on the distribution and timing of particular corbiculate groups, most notably the extension into North America of possible Eocene-Oligocene cooling-induced extinctions. Protohabropoda pauli De Meulemeester & Michez, gen. nov. sp. nov. (type species of Protohabropoda Dehon & Engel, n. gen.) reinforces previous hypotheses of anthophorine evolution in terms of ecological shifts by the Oligocene from tropical to mesic or xeric habitats. Lastly, a new fossil of the Andreninae, Andrena antoinei Michez & De Meulemeester, sp. nov., further documents the presence of the today widespread genus Andrena Fabricius in the Late Oligocene of France. 相似文献
98.
Odile Launay Anne Krivine Caroline Charlier Van Truster Vassilis Tsatsaris Jacques Lepercq Yves Ville Carolyn Avenell Thibaut Andrieu Flore Rozenberg Florence Artiguebielle Jean-Marc Tréluyer Fran?ois Goffinet Inserm COFLUPREG Study Group 《PloS one》2012,7(12)
Background
In 2009, pregnant women were specifically targeted by a national vaccination campaign against pandemic A/H1N1 influenza virus. The objectives of the COFLUPREG study, initially set up to assess the incidence of serious forms of A/H1N1 influenza, were to assess the consequences of maternal vaccination on pregnancy outcomes and maternal seroprotection at delivery.Methods
Pregnant women, between 12 and 35 weeks of gestation, non vaccinated against A/H1N1 2009 influenza were randomly selected to be included in a prospective cohort study conducted in three maternity centers in Paris (France) during pandemic period. Blood samples were planned to assess hemagglutination inhibition (HI) antibody against A/H1N1 2009 influenza at inclusion and at delivery.Results
Among the 877 pregnant women included in the study, 678 (77.3%) had serum samples both at inclusion and delivery, and 320 (36.5%) received pandemic A/H1N1 2009 influenza vaccine with a median interval between vaccination and delivery of 92 days (95% CI 48–134). At delivery, the proportion of women with seroprotection (HI antibodies titers against A/H1N1 2009 influenza of 1∶40 or greater) was 69.9% in vaccinated women. Of the 422 non-vaccinated women with serological data, 11 (2.6%; 95%CI: 1.3–4.6) had laboratory documented A/H1N1 2009 influenza (1 with positive PCR and 10 with serological seroconversion). None of the 877 study’s women was hospitalized for flu. No difference on pregnancy outcomes was evidenced between vaccinated women, non-vaccinated women without seroconversion and non-vaccinated women with flu.Conclusion
Despite low vaccine coverage, incidence of pandemic flu was low in this cohort of pregnant women.No effect on pregnancy and delivery outcomes was evidenced after vaccination. 相似文献99.
100.
Jombart T 《Bioinformatics (Oxford, England)》2008,24(11):1403-1405
The package adegenet for the R software is dedicated to the multivariate analysis of genetic markers. It extends the ade4 package of multivariate methods by implementing formal classes and functions to manipulate and analyse genetic markers. Data can be imported from common population genetics software and exported to other software and R packages. adegenet also implements standard population genetics tools along with more original approaches for spatial genetics and hybridization. AVAILABILITY: Stable version is available from CRAN: http://cran.r-project.org/mirrors.html. Development version is available from adegenet website: http://adegenet.r-forge.r-project.org/. Both versions can be installed directly from R. adegenet is distributed under the GNU General Public Licence (v.2). 相似文献