全文获取类型
收费全文 | 3112篇 |
免费 | 333篇 |
国内免费 | 2篇 |
出版年
2023年 | 18篇 |
2022年 | 44篇 |
2021年 | 73篇 |
2020年 | 47篇 |
2019年 | 57篇 |
2018年 | 57篇 |
2017年 | 59篇 |
2016年 | 90篇 |
2015年 | 168篇 |
2014年 | 214篇 |
2013年 | 190篇 |
2012年 | 297篇 |
2011年 | 303篇 |
2010年 | 181篇 |
2009年 | 150篇 |
2008年 | 213篇 |
2007年 | 180篇 |
2006年 | 173篇 |
2005年 | 173篇 |
2004年 | 150篇 |
2003年 | 119篇 |
2002年 | 119篇 |
2001年 | 31篇 |
2000年 | 23篇 |
1999年 | 22篇 |
1998年 | 30篇 |
1997年 | 12篇 |
1996年 | 18篇 |
1995年 | 21篇 |
1994年 | 14篇 |
1993年 | 14篇 |
1992年 | 13篇 |
1991年 | 9篇 |
1990年 | 16篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 4篇 |
1986年 | 13篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 4篇 |
1979年 | 10篇 |
1978年 | 8篇 |
1975年 | 4篇 |
1974年 | 9篇 |
1971年 | 3篇 |
1969年 | 5篇 |
排序方式: 共有3447条查询结果,搜索用时 0 毫秒
991.
Stability of pollination services decreases with isolation from natural areas despite honey bee visits 总被引:4,自引:0,他引:4
Garibaldi LA Steffan-Dewenter I Kremen C Morales JM Bommarco R Cunningham SA Carvalheiro LG Chacoff NP Dudenhöffer JH Greenleaf SS Holzschuh A Isaacs R Krewenka K Mandelik Y Mayfield MM Morandin LA Potts SG Ricketts TH Szentgyörgyi H Viana BF Westphal C Winfree R Klein AM 《Ecology letters》2011,14(10):1062-1072
Sustainable agricultural landscapes by definition provide high magnitude and stability of ecosystem services, biodiversity and crop productivity. However, few studies have considered landscape effects on the stability of ecosystem services. We tested whether isolation from florally diverse natural and semi-natural areas reduces the spatial and temporal stability of flower-visitor richness and pollination services in crop fields. We synthesised data from 29 studies with contrasting biomes, crop species and pollinator communities. Stability of flower-visitor richness, visitation rate (all insects except honey bees) and fruit set all decreased with distance from natural areas. At 1 km from adjacent natural areas, spatial stability decreased by 25, 16 and 9% for richness, visitation and fruit set, respectively, while temporal stability decreased by 39% for richness and 13% for visitation. Mean richness, visitation and fruit set also decreased with isolation, by 34, 27 and 16% at 1 km respectively. In contrast, honey bee visitation did not change with isolation and represented > 25% of crop visits in 21 studies. Therefore, wild pollinators are relevant for crop productivity and stability even when honey bees are abundant. Policies to preserve and restore natural areas in agricultural landscapes should enhance levels and reliability of pollination services. 相似文献
992.
Boggio KJ Obasuyi E Sugino K Nelson SB Agar NY Agar JN 《Expert review of proteomics》2011,8(5):591-604
Single-cell analysis is gaining popularity in the field of mass spectrometry as a method for analyzing protein and peptide content in cells. The spatial resolution of MALDI mass spectrometry (MS) imaging is by a large extent limited by the laser focal diameter and the displacement of analytes during matrix deposition. Owing to recent advancements in both laser optics and matrix deposition methods, spatial resolution on the order of a single eukaryotic cell is now achievable by MALDI MS imaging. Provided adequate instrument sensitivity, a lateral resolution of approximately 10 μm is currently attainable with commercial instruments. As a result of these advances, MALDI MS imaging is poised to become a transformative clinical technology. In this article, the crucial steps needed to obtain single-cell resolution are discussed, as well as potential applications to disease research. 相似文献
993.
994.
Sandell LL Iulianella A Melton KR Lynn M Walker M Inman KE Bhatt S Leroux-Berger M Crawford M Jones NC Dennis JF Trainor PA 《Genesis (New York, N.Y. : 2000)》2011,49(4):342-359
Proper craniofacial development begins during gastrulation and requires the coordinated integration of each germ layer tissue (ectoderm, mesoderm, and endoderm) and its derivatives in concert with the precise regulation of cell proliferation, migration, and differentiation. Neural crest cells, which are derived from ectoderm, are a migratory progenitor cell population that generates most of the cartilage, bone, and connective tissue of the head and face. Neural crest cell development is regulated by a combination of intrinsic cell autonomous signals acquired during their formation, balanced with extrinsic signals from tissues with which the neural crest cells interact during their migration and differentiation. Although craniofacial anomalies are typically attributed to defects in neural crest cell development, the cause may be intrinsic or extrinsic. Therefore, we performed a phenotype-driven ENU mutagenesis screen in mice with the aim of identifying novel alleles in an unbiased manner, that are critically required for early craniofacial development. Here we describe 10 new mutant lines, which exhibit phenotypes affecting frontonasal and pharyngeal arch patterning, neural and vascular development as well as sensory organ morphogenesis. Interestingly, our data imply that neural crest cells and endothelial cells may employ similar developmental programs and be interdependent during early embryogenesis, which collectively is critical for normal craniofacial morphogenesis. Furthermore our novel mutants that model human conditions such as exencephaly, craniorachischisis, DiGeorge, and Velocardiofacial sydnromes could be very useful in furthering our understanding of the complexities of specific human diseases. 相似文献
995.
An m.1630A>G mutation in the mitochondrial tRNA(Val) (MTTV) was identified in a patient with hearing impairment, short stature and new onset of stroke. This mutation has previously been identified in a patient with the mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). The mother of the proband also had high levels of the m.1630A>G allele present in blood and other tissues, without symptoms. To confirm the pathogenicity of this mutation, we created cybrid cell lines with various mutation loads. The m.1630A>G mutation impairs oxygen consumption, affects the stability of the MTTV and reduces the levels of subunits of the electron transport chain. 相似文献
996.
Frey S Sott K Smedh M Millat T Dahl P Wolkenhauer O Goksör M 《Molecular bioSystems》2011,7(1):215-223
Fluorescence microscopy is an imaging technique that provides insights into signal transduction pathways through the generation of quantitative data, such as the spatiotemporal distribution of GFP-tagged proteins in signaling pathways. The data acquired are, however, usually a composition of both the GFP-tagged proteins of interest and of an autofluorescent background, which both undergo photobleaching during imaging. We here present a mathematical model based on ordinary differential equations that successfully describes the shuttling of intracellular Mig1-GFP under changing environmental conditions regarding glucose concentration. Our analysis separates the different bleaching rates of Mig1-GFP and background, and the background-to-Mig1-GFP ratio. By applying our model to experimental data, we can thus extract the Mig1-GFP signal from the overall acquired signal and investigate the influence of kinase and phosphatase on Mig1. We found a stronger regulation of Mig1 through its kinase than through its phosphatase when controlled by the glucose concentration, with a constant (de)phosphorylation rate independent of the glucose concentration. By replacing the term for decreasing excited Mig1-GFP concentration with a constant, we were able to reconstruct the dynamics of Mig1-GFP, as it would occur without bleaching and background noise. Our model effectively demonstrates how data, acquired with an optical microscope, can be processed and used for a systems biology analysis of signal transduction pathways. 相似文献
997.
Ksepka DT Benton MJ Carrano MT Gandolfo MA Head JJ Hermsen EJ Joyce WG Lamm KS Patané JS Phillips MJ Polly PD Van Tuinen M Ware JL Warnock RC Parham JF 《Biology letters》2011,7(6):801-803
Divergence dating studies, which combine temporal data from the fossil record with branch length data from molecular phylogenetic trees, represent a rapidly expanding approach to understanding the history of life. National Evolutionary Synthesis Center hosted the first Fossil Calibrations Working Group (3-6 March, 2011, Durham, NC, USA), bringing together palaeontologists, molecular evolutionists and bioinformatics experts to present perspectives from disciplines that generate, model and use fossil calibration data. Presentations and discussions focused on channels for interdisciplinary collaboration, best practices for justifying, reporting and using fossil calibrations and roadblocks to synthesis of palaeontological and molecular data. Bioinformatics solutions were proposed, with the primary objective being a new database for vetted fossil calibrations with linkages to existing resources, targeted for a 2012 launch. 相似文献
998.
Werner K Rückert F Saeger HD Grützmann R Pilarsky C 《Recent patents on DNA & gene sequences》2011,5(1):28-34
Pancreatic cancer is one of the most malignant forms of cancer. Due to numerous defects of the apoptosis machinery this tumor shows a high resistance towards conventional oncological therapies. On the level of the extrinsic pathway, signal transduction is flawed by over-expression of decoy receptors but also by a dysfunctional death inducing signaling complex (DISC). The mitochondrial pathway, normally stimulated by cell stress and toxic agents is impeded by over-expression of anti-apoptotic members of the Bcl 2 protein family and the so-called inhibitor of apoptosis proteins (IAPs). To overcome the dysfunction of the apoptosis pathway, new therapeutics focus on molecular targets within the apoptosis pathway. Recently, many new treatment modalities have been reported like recombinant ligands of the cell death receptors or inhibitors of anti-apoptotic Bcl-2 members. Furthermore, various substances for the direct activation of the caspase cascade were patented and the over-expression of IAPs could be treated by binding inhibitors or using RNA interference techniques. The present review aims at giving an overview on these new treatment modalities. 相似文献
999.
Moffitt KL Gierahn TM Lu YJ Gouveia P Alderson M Flechtner JB Higgins DE Malley R 《Cell host & microbe》2011,9(2):158-165
Streptococcus pneumoniae is a leading cause of mortality in young children. While successful conjugate polysaccharide vaccines exist, a less expensive serotype-independent protein-based pneumococcal vaccine offers a major advancement for preventing life-threatening pneumococcal infections, particularly in developing nations. IL-17A-secreting CD4+ T cells (T(H)17) mediate resistance to mucosal colonization by multiple pathogens including S. pneumoniae. Screening an expression library containing >96% of predicted pneumococcal proteins, we identified antigens recognized by T(H)17 cells from mice immune to pneumococcal colonization. The identified antigens also elicited IL-17A secretion from colonized mouse splenocytes and human PBMCs suggesting that similar responses are primed during natural exposure. Immunization of two mouse strains with identified antigens provided protection from pneumococcal colonization that was significantly diminished in animals treated with blocking CD4 or IL-17A antibodies. This work demonstrates the potential of proteomic screening approaches to identify specific antigens for the design of subunit vaccines against mucosal pathogens via harnessing T(H)17-mediated immunity. 相似文献
1000.
Consumption of large amounts of fructose or sucrose increases lipogenesis and circulating triglycerides in humans. Although the underlying molecular mechanisms responsible for this effect are not completely understood, it is possible that as reported for rodents, high fructose exposure increases expression of the lipogenic enzymes fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC-1) in human liver. Since activation of the hexosamine biosynthesis pathway (HBP) is associated with increases in the expression of FAS and ACC-1, it raises the possibility that HBP-related metabolites would contribute to any increase in hepatic expression of these enzymes following fructose exposure. Thus, we compared lipogenic gene expression in human-derived HepG2 cells after incubation in culture medium containing glucose alone or glucose plus 5 mM fructose, using the HBP precursor 10 mM glucosamine (GlcN) as a positive control. Cellular metabolite profiling was conducted to analyze differences between glucose and fructose metabolism. Despite evidence for the active uptake and metabolism of fructose by HepG2 cells, expression of FAS or ACC-1 did not increase in these cells compared with those incubated with glucose alone. Levels of UDP-N-acetylglucosamine (UDP-GlcNAc), the end-product of the HBP, did not differ significantly between the glucose and fructose conditions. Exposure to 10 mM GlcN for 10 minutes to 24 hours resulted in 8-fold elevated levels of intracellular UDP-GlcNAc (P<0.001), as well as a 74-126% increase in FAS (P<0.05) and 49-95% increase in ACC-1 (P<0.01) expression above controls. It is concluded that in HepG2 liver cells cultured under standard conditions, sustained exposure to fructose does not result in an activation of the HBP or increased lipogenic gene expression. Should this scenario manifest in human liver in vivo, it would suggest that high fructose consumption promotes triglyceride synthesis primarily through its action to provide lipid precursor carbon and not by activating lipogenic gene expression. 相似文献