全文获取类型
收费全文 | 1930篇 |
免费 | 192篇 |
国内免费 | 1篇 |
专业分类
2123篇 |
出版年
2023年 | 13篇 |
2022年 | 36篇 |
2021年 | 62篇 |
2020年 | 25篇 |
2019年 | 37篇 |
2018年 | 47篇 |
2017年 | 40篇 |
2016年 | 61篇 |
2015年 | 104篇 |
2014年 | 133篇 |
2013年 | 150篇 |
2012年 | 190篇 |
2011年 | 159篇 |
2010年 | 107篇 |
2009年 | 96篇 |
2008年 | 119篇 |
2007年 | 97篇 |
2006年 | 95篇 |
2005年 | 102篇 |
2004年 | 71篇 |
2003年 | 63篇 |
2002年 | 56篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 15篇 |
1998年 | 14篇 |
1997年 | 8篇 |
1996年 | 6篇 |
1994年 | 12篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1986年 | 4篇 |
1984年 | 10篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 10篇 |
1973年 | 5篇 |
1970年 | 5篇 |
1969年 | 13篇 |
1968年 | 6篇 |
1967年 | 4篇 |
1960年 | 5篇 |
1958年 | 4篇 |
排序方式: 共有2123条查询结果,搜索用时 0 毫秒
71.
Catherine M. Phillips Audrey C. Tierney Pablo Perez‐Martinez Catherine Defoort Ellen E. Blaak Ingrid M. F. Gjelstad Jose Lopez‐Miranda Malgorzata Kiec‐Klimczak Malgorzata Malczewska‐Malec Christian A. Drevon Wendy Hall Julie A. Lovegrove Brita Karlstrom Ulf Risérus Helen M. Roche 《Obesity (Silver Spring, Md.)》2013,21(1):E154-E161
Objective:
Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study).Design and Methods:
Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n‐3 polyunsaturated fatty acids (LC n‐3 PUFAs)).Results:
About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (≥30 kg/m2) and BF% (≥25% (men) and ≥35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor‐1 (PAI‐1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA‐IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor‐α (TNF‐α) concentrations were lower post‐intervention in NOO individuals compared with OO subjects (P < 0.001).Conclusions:
In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone. 相似文献72.
Olivier Lambert Mélanie Piroux Sophie Puyo Chantal Thorin Monique L'Hostis Laure Wiest Audrey Buleté Frédéric Delbac Hervé Pouliquen 《PloS one》2013,8(6)
Background
The honey bee, Apis mellifera, is frequently used as a sentinel to monitor environmental pollution. In parallel, general weakening and unprecedented colony losses have been reported in Europe and the USA, and many factors are suspected to play a central role in these problems, including infection by pathogens, nutritional stress and pesticide poisoning. Honey bee, honey and pollen samples collected from eighteen apiaries of western France from four different landscape contexts during four different periods in 2008 and in 2009 were analyzed to evaluate the presence of pesticides and veterinary drug residues.Methodology/Findings
A multi-residue analysis of 80 compounds was performed using a modified QuEChERS method, followed by GC-ToF and LC−MS/MS. The analysis revealed that 95.7%, 72.3% and 58.6% of the honey, honey bee and pollen samples, respectively, were contaminated by at least one compound. The frequency of detection was higher in the honey samples (n = 28) than in the pollen (n = 23) or honey bee (n = 20) samples, but the highest concentrations were found in pollen. Although most compounds were rarely found, some of the contaminants reached high concentrations that might lead to adverse effects on bee health. The three most frequent residues were the widely used fungicide carbendazim and two acaricides, amitraz and coumaphos, that are used by beekeepers to control Varroa destructor. Apiaries in rural-cultivated landscapes were more contaminated than those in other landscape contexts, but the differences were not significant. The contamination of the different matrices was shown to be higher in early spring than in all other periods.Conclusions/Significance
Honey bees, honeys and pollens are appropriate sentinels for monitoring pesticide and veterinary drug environmental pollution. This study revealed the widespread occurrence of multiple residues in beehive matrices and suggests a potential issue with the effects of these residues alone or in combination on honey bee health. 相似文献73.
Trey K. Sato Mary Tremaine Lucas S. Parreiras Alexander S. Hebert Kevin S. Myers Alan J. Higbee Maria Sardi Sean J. McIlwain Irene M. Ong Rebecca J. Breuer Ragothaman Avanasi Narasimhan Mick A. McGee Quinn Dickinson Alex La Reau Dan Xie Mingyuan Tian Jeff S. Piotrowski Jennifer L. Reed Yaoping Zhang Joshua J. Coon Chris Todd Hittinger Audrey P. Gasch Robert Landick 《PLoS genetics》2016,12(11)
74.
75.
Audrey De Jong Pauline Deras Orianne Martinez Pascal Latry Samir Jaber Xavier Capdevila Jonathan Charbit 《PloS one》2016,11(3)
Background
Prediction of massive transfusion (MT) is challenging in management of trauma patients. However, MT and its prediction were poorly studied in obese patients. The main objective was to assess the relationship between obesity and MT needs in trauma patients. The secondary objectives were to validate the Trauma Associated Severe Hemorrhage (TASH) score in predicting MT in obese patients and to use a grey zone approach to optimize its ability to predict MT.Methods and Findings
An observational retrospective study was conducted in a Level I Regional Trauma Center Trauma in obese and non-obese patients. MT was defined as ≥10U of packed red blood cells in the first 24h and obesity as a BMI≥30kg/m². Between January 2008 and December 2012, 119 obese and 791 non-obese trauma patients were included. The rate of MT was 10% (94/910) in the whole population. The MT rate tended to be higher in obese patients than in non-obese patients: 15% (18/119, 95%CI 9‒23%) versus 10% (76/791, 95%CI 8‒12%), OR, 1.68 [95%CI 0.97‒2.92], p = 0.07. After adjusting for Injury Severity Score (ISS), obesity was significantly associated with MT rate (OR, 1.79[95%CI 1.00‒3.21], p = 0.049). The TASH score was higher in the obese group than in the non-obese group: 7(4–11) versus 5(2–10)(p<0.001). The area under the ROC curves of the TASH score in predicting MT was very high and comparable between the obese and non-obese groups: 0.93 (95%CI, 0.89‒0.98) and 0.94 (95%CI, 0.92‒0.96), respectively (p = 0.80). The grey zone ranged respectively from 10 to 13 and from 9 to 12 in obese and non obese patients, and allowed separating patients at low, intermediate or high risk of MT using the TASH score.Conclusions
Obesity was associated with a higher rate of MT in trauma patients. The predictive performance of the TASH score and the grey zones were robust and comparable between obese and non-obese patients. 相似文献76.
Coralie Coudray-Meunier Audrey Fraisse Sandra Martin-Latil Sabine Delannoy Patrick Fach Sylvie Perelle 《PloS one》2016,11(1)
Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log10. Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log10. Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log10 lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log10. Conversely, sensitivity was only 0.30 log10 better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health. 相似文献
77.
Ian Tagge Audrey O’Connor Priya Chaudhary Jim Pollaro Yosef Berlow Megan Chalupsky Dennis Bourdette Randy Woltjer Mac Johnson William Rooney 《PloS one》2016,11(4)
Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across time is essential for gaining a real understanding of disease processes in-vivo. MTR increases in healthy mice throughout adolescence and adulthood were observed, illustrating the need for appropriate age-matched controls. Elucidating the unique and site-specific demyelination in the cuprizone model may offer new insights into in mechanisms of both damage and repair in human demyelinating diseases. 相似文献
78.
79.
Alessandro Pagliuso Thibault Lagache Roger Persson Audrey Salles Jean‐Christophe Olivo‐Marin Stéphane Oddos Anne Spang Pascale Cossart Fabrizia Stavru 《EMBO reports》2016,17(6):858-873
Mitochondria are essential eukaryotic organelles often forming intricate networks. The overall network morphology is determined by mitochondrial fusion and fission. Among the multiple mechanisms that appear to regulate mitochondrial fission, the ER and actin have recently been shown to play an important role by mediating mitochondrial constriction and promoting the action of a key fission factor, the dynamin‐like protein Drp1. Here, we report that the cytoskeletal component septin 2 is involved in Drp1‐dependent mitochondrial fission in mammalian cells. Septin 2 localizes to a subset of mitochondrial constrictions and directly binds Drp1, as shown by immunoprecipitation of the endogenous proteins and by pulldown assays with recombinant proteins. Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP‐induced fission. Strikingly, septin depletion also affects mitochondrial morphology in Caenorhabditis elegans, strongly suggesting that the role of septins in mitochondrial dynamics is evolutionarily conserved. 相似文献
80.
Lise Pascale Alejandro López González Audrey Di Giorgio Marc Gaysinski Jordi Teixido Closa Roger Estrada Tejedor 《Journal of biomolecular structure & dynamics》2016,34(11):2327-2338
A series of pentameric “Polyamide Amino Acids” (PAAs) compounds derived from the same trimeric precursor have been synthesized and investigated as HIV TAR RNA ligands, in the absence and in the presence of a Tat fragment. All PAAs bind TAR with similar sub-micromolar affinities but their ability to compete efficiently with the Tat fragment strongly differs, IC50 ranging from 35 nM to >2 μM. While NMR and CD studies reveal that all PAA interact with TAR at the same site and induce globally the same RNA conformational change upon binding, a comparative thermodynamic study of PAA/TAR equilibria highlights distinct TAR binding modes for Tat competitor and non-competitor PAAs. This led us to suggest two distinct interaction modes that have been further validated by molecular modeling studies. While the binding of Tat competitor PAAs induces a contraction at the TAR bulge region, the binding of non-competitor ones widens it. This could account for the distinct PAA ability to compete with Tat fragment. Our work illustrates how comparative thermodynamic studies of a series of RNA ligands of same chemical family are of value for understanding their binding modes and for rationalizing structure-activity relationships. 相似文献