全文获取类型
收费全文 | 1818篇 |
免费 | 140篇 |
专业分类
1958篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 15篇 |
2021年 | 36篇 |
2020年 | 32篇 |
2019年 | 41篇 |
2018年 | 32篇 |
2017年 | 28篇 |
2016年 | 53篇 |
2015年 | 95篇 |
2014年 | 120篇 |
2013年 | 136篇 |
2012年 | 185篇 |
2011年 | 236篇 |
2010年 | 136篇 |
2009年 | 75篇 |
2008年 | 122篇 |
2007年 | 139篇 |
2006年 | 111篇 |
2005年 | 79篇 |
2004年 | 88篇 |
2003年 | 59篇 |
2002年 | 60篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 13篇 |
1998年 | 11篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1986年 | 1篇 |
排序方式: 共有1958条查询结果,搜索用时 15 毫秒
991.
Abt B Lu M Misra M Han C Nolan M Lucas S Hammon N Deshpande S Cheng JF Tapia R Goodwin L Pitluck S Liolios K Pagani I Ivanova N Mavromatis K Ovchinikova G Pati A Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Detter JC Brambilla E Rohde M Tindall BJ Göker M Woyke T Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2011,4(1):72-80
Cellulophaga algicola Bowman 2000 belongs to the family Flavobacteriaceae within the phylum 'Bacteroidetes' and was isolated from Melosira collected from the Eastern Antarctic coastal zone. The species is of interest because its members produce a wide range of extracellular enzymes capable of degrading proteins and polysaccharides with temperature optima of 20-30°C. This is the first completed genome sequence of a member of the genus Cellulophaga. The 4,888,353 bp long genome with its 4,285 protein-coding and 62 RNA genes consists of one circular chromosome and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
992.
993.
Background
Human Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease (HFMD) in young children. It is often associated with severe neurological diseases and has caused high mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no effective vaccine and antiviral agents available against EV71 infections. VP1 is one of the major immunogenic capsid protein of EV71 and plays a crucial role in viral infection. Antibodies against VP1 are important for virus neutralization.Methodology/Principal Finding
In the present study, infectious EV71 viruses were generated from their synthetic complementary DNA using the human RNA polymerase I reverse genetics system. Secondly, the major immunogenic capsid protein (VP1) of EV71-Fuyang (subgenogroup C4) was displayed on the surface of recombinant baculovirus Bac-Pie1-gp64-VP1 as gp64 fusion protein under a novel White Spot Syndrome Virus (WSSV) immediate early ie1 promoter. Baculovirus expressed VP1 was able to maintain its structural and antigenic conformity as indicated by immunofluorescence assay and western blot analysis. Interestingly, our results with confocal microscopy revealed that VP1 was able to localize on the plasma membrane of insect cells infected with recombinant baculovirus. In addition, we demonstrated with transmission electron microscopy that baculovirus successfully acquired VP1 from the insect cell membrane via the budding process. After two immunizations in mice, Bac-Pie1-gp64-VP1 elicited neutralization antibody titer of 1∶64 against EV71 (subgenogroup C4) in an in vitro neutralization assay. Furthermore, the antisera showed high cross-neutralization activities against all 11 subgenogroup EV71 strains.Conclusion
Our results illustrated that Bac-Pie1-gp64-VP1 retained native epitopes of VP1 and acted as an effective EV71 vaccine candidate which would enable rapid production without any biosafety concerns. 相似文献994.
Stadler T 《Systematic biology》2011,60(5):676-684
In this paper, I develop efficient tools to simulate trees with a fixed number of extant species. The tools are provided in my open source R-package TreeSim available on CRAN. The new model presented here is a constant rate birth-death process with mass extinction and/or rate shift events at arbitrarily fixed times 1) before the present or 2) after the origin. The simulation approach for case (2) can also be used to simulate under more general models with fixed events after the origin. I use the developed simulation tools for showing that a mass extinction event cannot be distinguished from a model with constant speciation and extinction rates interrupted by a phase of stasis based on trees consisting of only extant species. However, once we distinguish between mass extinction and period of stasis based on paleontological data, fast simulations of trees with a fixed number of species allow inference of speciation and extinction rates using approximate Bayesian computation and allow for robustness analysis once maximum likelihood parameter estimations are available. 相似文献
995.
The island rule states that small mammals isolated on islands have the evolutionary tendency to become larger, while large
mammals tend to become smaller. However, the underlying mechanisms and life history consequences of these insular shifts in
body size still remain speculative. The aim of this study was to investigate whether an arboreal mammal, the edible dormouse
(Glis glis), showed shifts in body size when inhabiting isolated forest fragments. We analysed a data set of 541 individuals captured
between 2005 and 2010 in four different forest fragments and one continuous forest, which served as a reference area. Sex,
age, body mass, and size of all individuals were known. We used linear mixed-effect models to investigate whether individuals
differed in their body size and mass between forest fragments and continuous forest. Our study revealed that edible dormice
inhabiting forest fragments were significantly larger and heavier than individuals in the continuous forest, in accordance
with patterns described by the island rule for small mammals. Because edible dormice frequently use nest boxes to rest during
the day and to rear offspring, the life history strategies of this rodent can be easily investigated under evolutionary relevant
conditions in the field. Thus the edible dormouse represents an excellent model organism for studying the mechanisms underlying
shifts in body size as a response to habitat fragmentation and to investigate the consequences of these shifts on their life
history strategies. 相似文献
996.
997.
Etienne RS Haegeman B Stadler T Aze T Pearson PN Purvis A Phillimore AB 《Proceedings. Biological sciences / The Royal Society》2012,279(1732):1300-1309
The branching times of molecular phylogenies allow us to infer speciation and extinction dynamics even when fossils are absent. Troublingly, phylogenetic approaches usually return estimates of zero extinction, conflicting with fossil evidence. Phylogenies and fossils do agree, however, that there are often limits to diversity. Here, we present a general approach to evaluate the likelihood of a phylogeny under a model that accommodates diversity-dependence and extinction. We find, by likelihood maximization, that extinction is estimated most precisely if the rate of increase in the number of lineages in the phylogeny saturates towards the present or first decreases and then increases. We demonstrate the utility and limits of our approach by applying it to the phylogenies for two cases where a fossil record exists (Cetacea and Cenozoic macroperforate planktonic foraminifera) and to three radiations lacking fossil evidence (Dendroica, Plethodon and Heliconius). We propose that the diversity-dependence model with extinction be used as the standard model for macro-evolutionary dynamics because of its biological realism and flexibility. 相似文献
998.
U Junius-Walker J Wrede T Schleef H Diederichs-Egidi B Wiese E Hummers-Pradier ML Dierks 《BMC research notes》2012,5(1):443
ABSTRACT: BACKGROUND: GPs increasingly deal with multiple health problems of their older patients. They have to apply a hierarchical management approach that considers priorities to balance competing needs for treatment. Yet, the practice of setting individual priorities in older patients is largely unexplored. This paper analyses the GPs' perceptions on important and unimportant health problems and how these affect their treatment. METHODS: GPs appraised the importance of health problems for a purposive sample of their older patients in semi-structured interviews. Prior to the interviews, the GPs had received a list of their patients' health problems resulting from a geriatric assessment and were asked to rate the importance of each identified problem. In the interviews the GPs subsequently explained why they considered certain health problems important or not and how this affected treatment. Data was analysed using qualitative content analysis and quantitative methods. RESULTS: The problems GPs perceive as important are those that are medical and require active treatment or monitoring, or that induce empathy or awareness but cannot be assisted further. Unimportant problems are those that are well managed problems and need no further attention as well as age-related conditions or functional disabilities that provoke fatalism, or those considered outside the GPs' responsibility. Statements of professional actions are closely linked to explanations of important problems and relate to physical problems rather than functional and social patient issues. CONCLUSIONS: GPs tend to prioritise treatable clinical conditions. Treatment approaches are, however, vague or missing for complex chronic illnesses and disabilities. Here, patient empowerment strategies are of value and need to be developed and implemented. The professional concepts of ageing and disability should not impede but rather foster treatment and care. To this end, GPs need to be able to delegate care to a functioning primary care team. Trial Registration German Trial Register (DRKS): 00000792. 相似文献
999.
Microvascular and mitochondrial PO2 simultaneously measured by oxygen‐dependent delayed luminescence
Sander I. A. Bodmer Gianmarco M. Balestra Floor A. Harms Tanja Johannes Nicolaas J. H. Raat Robert J. Stolker Egbert G. Mik 《Journal of biophotonics》2012,5(2):140-151
Measurement of tissue oxygenation is a complex task and various techniques have led to a wide range of tissue PO2 values and contradictory results. Tissue is compartmentalized in microcirculation, interstitium and intracellular space and current techniques are biased towards a certain compartment. Simultaneous oxygen measurements in various compartments might be of great benefit for our understanding of determinants of tissue oxygenation. Here we report simultaneous measurement of microvascular PO2 (μPO2) and mitochondrial PO2 (mitoPO2) in rats. The μPO2 measurements are based on oxygen‐dependent quenching of phosphorescence of the near‐infrared phosphor Oxyphor G2. The mitoPO2 measurements are based on oxygen‐dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Favorable spectral properties of these porphyrins allow simultaneous measurement of the delayed luminescence lifetimes. A dedicated fiber‐based time‐domain setup consisting of a tunable pulsed laser, 2 red‐sensitive gated photomultiplier tubes and a simultaneous sampling data‐acquisition system is described in detail. The absence of cross talk between the channels is shown and the feasibility of simultaneous μPO2 and mitoPO2 measurements is demonstrated in rat liver in vivo. It is anticipated that this novel approach will greatly contribute to our understanding of tissue oxygenation in physiological and pathological circumstances. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
1000.
Scherag A Kleber M Boes T Kolbe AL Ruth A Grallert H Illig T Heid IM Toschke AM Grau K;NUGENOB Consortium Sørensen TI Hebebrand J Hinney A Reinehr T 《Obesity (Silver Spring, Md.)》2012,20(2):466-470
Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention. 相似文献