全文获取类型
收费全文 | 1330篇 |
免费 | 84篇 |
出版年
2023年 | 7篇 |
2022年 | 24篇 |
2021年 | 40篇 |
2020年 | 24篇 |
2019年 | 23篇 |
2018年 | 24篇 |
2017年 | 14篇 |
2016年 | 46篇 |
2015年 | 81篇 |
2014年 | 81篇 |
2013年 | 84篇 |
2012年 | 70篇 |
2011年 | 106篇 |
2010年 | 56篇 |
2009年 | 56篇 |
2008年 | 73篇 |
2007年 | 79篇 |
2006年 | 60篇 |
2005年 | 56篇 |
2004年 | 45篇 |
2003年 | 48篇 |
2002年 | 44篇 |
2001年 | 19篇 |
2000年 | 19篇 |
1999年 | 21篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 15篇 |
1991年 | 13篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1980年 | 9篇 |
1978年 | 5篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1969年 | 3篇 |
1967年 | 3篇 |
1966年 | 5篇 |
1965年 | 3篇 |
1961年 | 3篇 |
排序方式: 共有1414条查询结果,搜索用时 31 毫秒
101.
Nanikaly Moyen Laurence Thirion Petra Emmerich Amelia Dzia-Lepfoundzou Hervé Richet Yannik Boehmann Yannick Dimi Pierre Gallian Ernest A. Gould Stephan Günther Xavier de Lamballerie 《PLoS neglected tropical diseases》2015,9(6)
BackgroundEbola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV.Conclusions/SignificanceThis MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors. 相似文献
102.
Terence Tafatatha Miriam Taegtmeyer Bagrey Ngwira Amos Phiri Mariot Kondowe Wilson Piston Anna Molesworth Ndoliwe Kayuni Olivier Koole Amelia Crampin John Horton Neil French 《PLoS neglected tropical diseases》2015,9(6)
BackgroundLymphatic filariasis (LF) and human immunodeficiency virus (HIV) are major public health problems. Individuals may be co-infected, raising the possibility of important interactions between these two pathogens with consequences for LF elimination through annual mass drug administration (MDA).Conclusions/SignificanceIn this large cross-sectional study of two distinct LF-exposed populations, there is no evidence that HIV infection has an impact on LF epidemiology that will interfere with LF control measures. A significant association of ART use with lower CFA prevalence merits further investigation to understand this apparent beneficial impact of ART. 相似文献
103.
Mariapaola Marino Flavia Scuderi Daniela Samengo Giorgia Saltelli Maria Teresa Maiuri Chengyong Shen Lin Mei Mario Sabatelli Giovambattista Pani Giovanni Antonini Amelia Evoli Emanuela Bartoccioni 《PloS one》2015,10(8)
Background
Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoantibodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4 (LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG.Methods
The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system.Results
We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals.Conclusion
Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis. 相似文献104.
Christophe Marti Olivier Grosgurin Stephan Harbarth Christophe Combescure Mohamed Abbas Olivier Rutschmann Arnaud Perrier Nicolas Garin 《PloS one》2015,10(12)
Background
Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP.Methods
We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications.Results
14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96).Conclusion
Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain. 相似文献105.
106.
Melanie Brügger Thomas Dmoulins G. Tuba Barut Beatrice Zumkehr Blandina I. Oliveira Esteves Kemal Mehinagic Quentin Haas Aline Schgler Marie-Anne Rameix-Welti Jean-Franois Elouët Ueli Moehrlen Thomas M. Marti Ralph A. Schmid Artur Summerfield Horst Posthaus Nicolas Ruggli Sean R. R. Hall Marco P. Alves 《PLoS pathogens》2021,17(7)
107.
Alison Donnelly Olivia Crowe Eugenie Regan Sinead Begley Amelia Caffarra 《International journal of biometeorology》2014,58(6):1237-1249
Citizen science is proving to be an effective tool in tracking the rapid pace at which our environment is changing over large geographic areas. It is becoming increasingly popular, in places such as North America and some European countries, to engage members of the general public and school pupils in the collection of scientific data to support long-term environmental monitoring. Participants in such schemes are generally volunteers and are referred to as citizen scientists. The Christmas bird count in the US is one of the worlds longest running citizen science projects whereby volunteers have been collecting data on birds on a specific day since 1900. Similar volunteer networks in Ireland have been in existence since the 1960s and were established to monitor the number and diversity of birds throughout the country. More recently, initiatives such as Greenwave (2006) and Nature Watch (2009) invite school children and members of the general public respectively, to record phenology data from a range of common species of plant, insect and bird. In addition, the Irish butterfly and bumblebee monitoring schemes engage volunteers to record data on sightings of these species. The primary purpose of all of these networks is to collect data by which to monitor changes in wildlife development and diversity, and in the case of Greenwave to involve children in hands-on, inquiry-based science. Together these various networks help raise awareness of key environmental issues, such as climate change and loss of biodiversity, while at the same time promote development of scientific skills among the general population. In addition, they provide valuable scientific data by which to track environmental change. Here we examine the role of citizen science in monitoring biodiversity in Ireland and conclude that some of the data collected in these networks can be used to fulfil Ireland’s statutory obligations for nature conservation. In addition, a bee thought previously to be extinct has been rediscovered and a range expansion of a different bee has been confirmed. However, it also became apparent that some of the networks play more of an educational than a scientific role. Furthermore, we draw on experience from a range of citizen science projects to make recommendations on how best to establish new citizen science projects in Ireland and strengthen existing ones. 相似文献
108.
Leonardo Boechi Pau Arroyo Mañez F. Javier Luque Marcelo A. Marti Dario A. Estrin 《Proteins》2010,78(4):962-970
Truncated hemoglobins (trHbs) are heme proteins present in bacteria, unicellular eukaryotes, and higher plants. Their tertiary structure consists in a 2‐over‐2 helical sandwich, which display typically an inner tunnel/cavity system for ligand migration and/or storage. The microorganism Bacillus subtilis contains a peculiar trHb, which does not show an evident tunnel/cavity system connecting the protein active site with the solvent, and exhibits anyway a very high oxygen association rate. Moreover, resonant Raman results of CO bound protein, showed that a complex hydrogen bond network exists in the distal cavity, making it difficult to assign unambiguously the residues involved in the stabilization of the bound ligand. To understand these experimental results with atomistic detail, we performed classical molecular dynamics simulations of the oxy, carboxy, and deoxy proteins. The free energy profiles for ligand migration suggest that there is a key residue, GlnE11, that presents an alternate conformation, in which a wide ligand migration tunnel is formed, consistently with the kinetic data. This tunnel is topologically related to the one found in group I trHbs. On the other hand, the results for the CO and O2 bound protein show that GlnE11 is directly involved in the stabilization of the cordinated ligand, playing a similar role as TyrB10 and TrpG8 in other trHbs. Our results not only reconcile the structural data with the kinetic information, but also provide additional insight into the general behaviour of trHbs. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献
109.
Lucia Marti Giovanni Stefano Kentaro Tamura Chris Hawes Luciana Renna Michael A. Held Federica Brandizzi 《The Plant journal : for cell and molecular biology》2010,63(6):901-913
A central question in cell biology is how the identity of organelles is established and maintained. Here, we report on GOLD36, an EMS mutant identified through a screen for partial displacement of the Golgi marker, ST‐GFP, to other organelles. GOLD36 showed partial distribution of ST‐GFP into a modified endoplasmic reticulum (ER) network, which formed bulges and large skein‐like structures entangling Golgi stacks. GOLD36 showed defects in ER protein export as evidenced by our observations that, besides the partial retention of Golgi markers in the ER, the trafficking of a soluble bulk‐flow marker to the cell surface was also compromised. Using a combination of classical mapping and next‐generation DNA sequencing approaches, we linked the mutant phenotype to a missense mutation of a proline residue in position 80 to a leucine residue in a small endomembrane protein encoded by the gold36 locus ( At1g54030 ). Subcellular localization analyses indicated that GOLD36 is a vacuolar protein and that its mutated form is retained in the ER. Interestingly also, a gold36 knock‐out mutant mirrored the GOLD36 subcellular phenotype. These data indicate that GOLD36 is a protein destined to post‐ER compartments and suggest that its export from the ER is a requirement to ensure steady‐state maintenance of the organelle’s organization and functional activity in relation to other secretory compartments. We speculate that GOLD36 may be a factor that is necessary for ER integrity because of its ability to limit deleterious effects of other secretory proteins on the ER. 相似文献
110.
Ismael Bustos-Jaimes Rodrigo Mora-Lugo Mario L. Calcagno Amelia Farrés 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(12):2222-2227
Lipases are useful catalysts for a wide variety of industrial purposes. Herein we report the stability and thermal dependence of the activity of wild-type Bacillus pumilus lipase (BplA) and four site-directed mutants designed to improve its thermal stability. The Gly28:Ser mutation produces a dramatic four-fold increase in its kcat and a remarkable increase in its stability. While the increase in kcat is temperature-independent, the increase in stability shows that the resultant interactions of this mutation have a strong enthalpic component. Thermal dependence of stability, kcat, KM and kcat/KM were analysed to gain insight on the structural effects of mutations on BplA. Our results are consistent with a gain in enzyme mobility for those mutants displaying enhanced catalytic properties; the analysis of thermal dependence of kinetic parameters indicates that the mutations did not change either the catalytic mechanism or the rate-limiting step of catalysis. 相似文献