全文获取类型
收费全文 | 6827篇 |
免费 | 483篇 |
国内免费 | 1篇 |
出版年
2024年 | 6篇 |
2023年 | 40篇 |
2022年 | 115篇 |
2021年 | 181篇 |
2020年 | 138篇 |
2019年 | 163篇 |
2018年 | 209篇 |
2017年 | 160篇 |
2016年 | 281篇 |
2015年 | 449篇 |
2014年 | 437篇 |
2013年 | 571篇 |
2012年 | 650篇 |
2011年 | 624篇 |
2010年 | 341篇 |
2009年 | 310篇 |
2008年 | 389篇 |
2007年 | 369篇 |
2006年 | 333篇 |
2005年 | 301篇 |
2004年 | 257篇 |
2003年 | 211篇 |
2002年 | 234篇 |
2001年 | 41篇 |
2000年 | 28篇 |
1999年 | 40篇 |
1998年 | 53篇 |
1997年 | 28篇 |
1996年 | 34篇 |
1995年 | 23篇 |
1994年 | 28篇 |
1993年 | 22篇 |
1992年 | 27篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 13篇 |
1985年 | 9篇 |
1984年 | 13篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 13篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1976年 | 5篇 |
1974年 | 6篇 |
1973年 | 14篇 |
排序方式: 共有7311条查询结果,搜索用时 15 毫秒
61.
The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine. 相似文献
62.
Marta Marchetti Delphine Capela Renaud Poincloux Nacer Benmeradi Marie-Christine Auriac Aurélie Le Ru Isabelle Maridonneau-Parini Jacques Batut Catherine Masson-Boivin 《PloS one》2013,8(2)
Rhizobia are symbiotic soil bacteria able to intracellularly colonize legume nodule cells and form nitrogen-fixing symbiosomes therein. How the plant cell cytoskeleton reorganizes in response to rhizobium colonization has remained poorly understood especially because of the lack of an in vitro infection assay. Here, we report on the use of the heterologous HeLa cell model to experimentally tackle this question. We observed that the model rhizobium Sinorhizobium meliloti, and other rhizobia as well, were able to trigger a major reorganization of actin cytoskeleton of cultured HeLa cells in vitro. Cell deformation was associated with an inhibition of the three major small RhoGTPases Cdc42, RhoA and Rac1. Bacterial entry, cytoskeleton rearrangements and modulation of RhoGTPase activity required an intact S. meliloti biosynthetic pathway for queuosine, a hypermodifed nucleoside regulating protein translation through tRNA, and possibly mRNA, modification. We showed that an intact bacterial queuosine biosynthetic pathway was also required for effective nitrogen-fixing symbiosis of S. meliloti with its host plant Medicago truncatula, thus indicating that one or several key symbiotic functions of S. meliloti are under queuosine control. We discuss whether the symbiotic defect of que mutants may originate, at least in part, from an altered capacity to modify plant cell actin cytoskeleton. 相似文献
63.
64.
Marta Castro Lizet Sánchez Dennis Pérez Carlos Sebrango Ziv Shkedy Patrick Van der Stuyft 《PloS one》2013,8(12)
The reemergence of dengue as an important public health problem reflects the difficulties in sustaining vertically organized, effective, control programs and the need for community-based strategies for Aedes aegypti control that result in behavioral change. We aimed to disentangle the relationships between underlying determinants of dengue related practices. We conducted a cross-sectional study in 780 households in La Lisa, Havana, Cuba. A questionnaire and an observation guide were administrated to collect information on variables related to economic status, knowledge on dengue, risk perception and practices associated with Aedes aegypti breading sites. To test a conceptual model that hypothesized direct relationships among all these constructs, we first used Exploratory Factor Analysis with Principal Component Analysis to establish the relationship between observed variables and the underlying latent variables. Subsequently, we tested whether the observed data supported the conceptual model through Confirmatory Factor Analysis. Exploratory Factor Analysis indicated that the items measured could be reduced into five factors with an eigenvalue >1.0: Knowledge on dengue, Intradomiciliar risk practices, Peridomiciliar risk practices, Risk perception and Economic status. The proportion of the total variance in the data explained by these five factors was 74.3%. The Confirmatory Factor Analysis model differed from our hypothesized conceptual model. Only Knowledge on dengue had a significant, direct, positive, effect on Practices. There was also a direct association of Economic status with Knowledge on dengue, but not with Risk perception and Practices. Clarifying the relationship between direct and indirect determinants of dengue related practices contributes to a better understanding of the potential effect of Information Education and Communication on practices and on the reduction of Aedes aegypti breeding sites and provides inputs for designing a community based strategy for dengue control. 相似文献
65.
66.
Bączyk Justyna Gogiel Tomasz Wolańska Małgorzata Bruczko Marta Guszczyn Tomasz Popko Janusz Romanowicz Lech 《International journal of peptide research and therapeutics》2020,26(1):271-280
International Journal of Peptide Research and Therapeutics - The progressive damage of human articular cartilage is associated with loss of integrity of its extracellular matrix components. Their... 相似文献
67.
David García‐Bernal Marta Palomo Carlos M. Martínez Jos E. Milln‐Rivero Ana I. García‐Guilln Miguel Blanquer Maribel Díaz‐Ricart Robert Sackstein Enric Carreras Jose M. Moraleda 《Journal of cellular and molecular medicine》2020,24(14):8031-8044
Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is an effective therapy for the treatment of high‐risk haematological malignant disorders and other life‐threatening haematological and genetic diseases. Acute graft‐versus‐host disease (aGvHD) remains the most frequent cause of non‐relapse mortality following allo‐HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi‐target drug successfully employed for prophylaxis and treatment of veno‐occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo‐HCT. Using a fully MHC‐mismatched murine model of allo‐HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD‐associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo‐HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte‐endothelial interactions by down‐regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo‐HCT, paving the way for new therapeutic approaches. 相似文献
68.
Scott Klasek Marta E. Torres Douglas H. Bartlett Madeline Tyler Wei-Li Hong Frederick Colwell 《Environmental microbiology》2020,22(5):1829-1846
Anaerobic methanotrophic archaea (ANME) consume methane in marine sediments, limiting its release to the water column, but their responses to changes in methane and sulfate supplies remain poorly constrained. To address how methane exposure may affect microbial communities and methane- and sulfur-cycling gene abundances in Arctic marine sediments, we collected sediments from offshore Svalbard that represent geochemical horizons where anaerobic methanotrophy is expected to be active, previously active, and long-inactive based on reaction-transport biogeochemical modelling of porewater sulfate profiles. Sediment slurries were incubated at in situ temperature and pressure with different added methane concentrations. Sediments from an active area of seepage began to reduce sulfate in a methane-dependent manner within months, preceding increased relative abundances of anaerobic methanotrophs ANME-1 within communities. In previously active and long-inactive sediments, sulfur-cycling Deltaproteobacteria became more dominant after 30 days, though these communities showed no evidence of methanotrophy after nearly 8 months of enrichment. Overall, enrichment conditions, but not methane, broadly altered microbial community structure across different enrichment times and sediment types. These results suggest that active ANME populations may require years to develop, and consequently microbial community composition may affect methanotrophic responses to potential large-scale seafloor methane releases in ways that provide insight for future modelling studies. 相似文献
69.
Tina Wagner Lara Prez-Martínez Ren Schellhaas Marta Barrientos-Moreno Merve
ztürk Flix Prado Falk Butter Brian Luke 《PLoS genetics》2020,16(12)
Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence. 相似文献
70.
Grazia Maria Cappucci Martina Pini Paolo Neri Marta Marassi Elena Bassoli Anna Maria Ferrari 《Journal of Industrial Ecology》2020,24(3):681-694
Additive manufacturing consists in melting metallic powders to produce objects from 3D data, layer upon layer. Its industrial applications range from automotive, biomedical (e.g., prosthetic implants for dentistry and orthopedics), aeronautics and others. This study uses life cycle assessment to evaluate the possible improvement in environmental performance of laser‐based powder bed fusion additive manufacturing systems on prosthetic device production. Environmental impacts due to manufacturing, use, and end of life of the designed solution were assessed. In addition, two powder production technologies, gas atomization (GA) and plasma atomization (PA), were compared in order to establish the most sustainable one. Production via traditional subtractive technologies and the additive manufacturing production were also compared. 3D building was found to have a significant environmental advantage compared to the traditional technology. The powder production process considerably influences on a damage point of view the additive manufacturing process; however, its impact can be mitigated if GA powders are employed. 相似文献