全文获取类型
收费全文 | 2047篇 |
免费 | 140篇 |
国内免费 | 1篇 |
专业分类
2188篇 |
出版年
2023年 | 8篇 |
2022年 | 28篇 |
2021年 | 35篇 |
2020年 | 33篇 |
2019年 | 39篇 |
2018年 | 59篇 |
2017年 | 39篇 |
2016年 | 67篇 |
2015年 | 97篇 |
2014年 | 116篇 |
2013年 | 134篇 |
2012年 | 177篇 |
2011年 | 144篇 |
2010年 | 99篇 |
2009年 | 88篇 |
2008年 | 120篇 |
2007年 | 130篇 |
2006年 | 121篇 |
2005年 | 104篇 |
2004年 | 83篇 |
2003年 | 66篇 |
2002年 | 67篇 |
2001年 | 20篇 |
2000年 | 14篇 |
1999年 | 24篇 |
1998年 | 21篇 |
1997年 | 17篇 |
1996年 | 17篇 |
1995年 | 12篇 |
1994年 | 14篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 6篇 |
1975年 | 6篇 |
1970年 | 5篇 |
1968年 | 6篇 |
1967年 | 6篇 |
排序方式: 共有2188条查询结果,搜索用时 15 毫秒
31.
Isabela P. Gomes Talita L. Santos Amanda N. de Souza Lúcio O. Nunes Gabriele A. Cardoso Carolina O. Matos Lívia M.F. Costa Luciano M. Lião Jarbas M. Resende Rodrigo M. Verly 《生物化学与生物物理学报:生物膜》2021,1863(1):183449
Studies have suggested that antimicrobial peptides act by different mechanisms, such as micellisation, self-assembly of nanostructures and pore formation on the membrane surface. This work presents an extensive investigation of the membrane interactions of the 14 amino-acid antimicrobial peptide hylaseptin P1-NH2 (HSP1-NH2), derived from the tree-frog Hyla punctata, which has stronger antifungal than antibacterial potential. Biophysical and structural analyses were performed and the correlated results were used to describe in detail the interactions of HSP1-NH2 with zwitterionic and anionic detergent micelles and phospholipid vesicles. HSP1-NH2 presents similar well-defined helical conformations in both zwitterionic and anionic micelles, although NMR spectroscopy revealed important structural differences in the peptide N-terminus. 2H exchange experiments of HSP1-NH2 indicated the insertion of the most N-terminal residues (1–3) in the DPC-d38 micelles. A higher enthalpic contribution was verified for the interaction of the peptide with anionic vesicles in comparison with zwitterionic vesicles. The pore formation ability of HSP1-NH2 (examined by dye release assays) and its effect on the size and surface charge as well as on the lipid acyl chain ordering (evaluated by Fourier-transform infrared spectroscopy) of anionic phospholipid vesicles showed membrane disruption even at low peptide-to-phospholipid ratios, and the effect increases proportionately to the peptide concentration. On the other hand, these biophysical investigations showed that a critical peptide-to-phospholipid ratio around 0.6 is essential for promoting disruption of zwitterionic membranes. In conclusion, this study demonstrates that the binding process of the antimicrobial HSP1-NH2 peptide depends on the membrane composition and peptide concentration. 相似文献
32.
Olívia Moraes Ruberti Andressa Silva Sousa Laís Rosa Viana Moiss Felipe Pereira Gomes Alessandra Medeiros Maria Cristina Cintra Gomes Marcondes Luciano de Figueiredo Borges Carlos Cesar Crestani Cristiano Mostarda Telma Ftima da Cunha Moraes Rafael Renatino Canevarolo Maria Andreia Delbin Bruno Rodrigues 《Journal of cellular physiology》2021,236(2):1105-1115
This study aimed to evaluate the impact of aerobic training (AT) on autonomic, cardiometabolic, ubiquitin‐proteasome activity, and inflammatory changes evoked by myocardial infarction (MI) in ovariectomized rats. Female Wistar rats were ovariectomized and divided into four groups: sedentary + sham (SS), sedentary + MI (SI), AT + sham surgery (TS), AT + MI (TI). AT was performed on a treadmill for 8 weeks before MI. Infarcted rats previously subjected to AT presented improved physical capacity, increased interleukin‐10, and decreased pro‐inflammatory cytokines. Metabolomic analysis identified and quantified 62 metabolites, 9 were considered significant by the Vip Score. SS, SI, and TS groups presented distinct metabolic profiles; however, TI could not be distinguished from the SS group. MI dramatically increased levels of dimethylamine, and AT prevented this response. Our findings suggest that AT may be useful in preventing the negative changes in functional, inflammatory, and metabolic parameters related to MI in ovariectomized rats. 相似文献
33.
Mariana Morando Luciano J. Avila Cristian H.F. Perez Monty A. Hawkins Jack W. Sites 《Molecular phylogenetics and evolution》2013,66(3):694-714
The lizard genus Phymaturus is widely distributed in Argentina and along the eastern edge of Chile between 25° and 45° south. We sampled 27 of the 38 currently recognized species plus 22 candidate species using two mitochondrial genes (cytb and 12S), four protein coding nuclear genes and seven anonymous nuclear loci, and present the first comprehensive molecular phylogenetic hypothesis for the clade. We recovered two large clades (the palluma or northern group and patagonicus or southern group) previously recognized on the basis of morphological and mitochondrial sequence evidence, and compared results obtained from concatenated-gene analyses with results of a coalescent-based species-tree approach (BEST). With both methods we identified four main clades within the palluma group (mallimaccii, roigorum, verdugo, and vociferator) and five main clades within the patagonicus group (calcogaster, indistinctus, payuniae, somuncurensis, and spurcus). We found several instances of non-monophyly with cytb and cases of incongruence between mitochondrial vs nuclear data for which we discuss alternative hypotheses. Although with lower support values, combined BEST results are more congruent with concatenated nuclear data than with combined concatenated analyses, suggesting that BEST is less influenced by demographic processes than combined concatenated analyses. We discuss the taxonomic, biogeographic and conservation implications of these results and how the future integration of phylogeographic and morphological approaches will allow the further testing of demographic and biogeographic hypotheses. 相似文献
34.
35.
36.
37.
Chris J. Brauer Peter J. Unmack Michael P. Hammer Mark Adams Luciano B. Beheregaray 《PloS one》2013,8(12)
Habitat fragmentation caused by human activities alters metapopulation dynamics and decreases biological connectivity through reduced migration and gene flow, leading to lowered levels of population genetic diversity and to local extinctions. The threatened Yarra pygmy perch, Nannoperca obscura, is a poor disperser found in small, isolated populations in wetlands and streams of southeastern Australia. Modifications to natural flow regimes in anthropogenically-impacted river systems have recently reduced the amount of habitat for this species and likely further limited its opportunity to disperse. We employed highly resolving microsatellite DNA markers to assess genetic variation, population structure and the spatial scale that dispersal takes place across the distribution of this freshwater fish and used this information to identify conservation units for management. The levels of genetic variation found for N. obscura are amongst the lowest reported for a fish species (mean heterozygosity of 0.318 and mean allelic richness of 1.92). We identified very strong population genetic structure, nil to little evidence of recent migration among demes and a minimum of 11 units for conservation management, hierarchically nested within four major genetic lineages. A combination of spatial analytical methods revealed hierarchical genetic structure corresponding with catchment boundaries and also demonstrated significant isolation by riverine distance. Our findings have implications for the national recovery plan of this species by demonstrating that N. obscura populations should be managed at a catchment level and highlighting the need to restore habitat and avoid further alteration of the natural hydrology. 相似文献
38.
M. Luciano D. M. Evans N. K. Hansell S. E. Medland G. W. Montgomery N. G. Martin M. J. Wright T. C. Bates 《Genes, Brain & Behavior》2013,12(6):645-652
Candidate genes have been identified for both reading and language, but most of the heritable variance in these traits remains unexplained. Here, we report a genome‐wide association meta‐analysis of two large cohorts: population samples of Australian twins and siblings aged 12–25 years (n = 1177 from 538 families), and a younger cohort of children of the UK Avon Longitudinal Study of Parents and their Children (aged 8 and 9 years; maximum n = 5472). Suggestive association was indicated for reading measures and non‐word repetition (NWR), with the greatest support found for single nucleotide polymorphisms (SNPs) in the pseudogene, ABCC13 (P = 7.34 × 10?8), and the gene, DAZAP1 (P = 1.32 × 10?6). Gene‐based analyses showed significant association (P < 2.8 × 10?6) for reading and spelling with genes CD2L1, CDC2L2 and RCAN3 in two loci on chromosome 1. Some support was found for the same SNPs having effects on both reading skill and NWR, which is compatible with behavior genetic evidence for influences of reading acquisition on phonological‐task performance. The results implicate novel candidates for study in additional cohorts for reading and language abilities. 相似文献
39.
40.
Mariarosaria Calvello Silvia Tabano Patrizia Colapietro Silvia Maitz Alessandra Pansa Claudia Augello Faustina Lalatta Barbara Gentilin Filippo Spreafico Luciano Calzari Daniela Perotti Lidia Larizza Silvia Russo Angelo Selicorni Silvia M Sirchia Monica Miozzo 《Epigenetics》2013,8(10):1053-1060
Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p < 0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75–86%) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55–59%) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD. 相似文献