全文获取类型
收费全文 | 487篇 |
免费 | 30篇 |
出版年
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 13篇 |
2020年 | 12篇 |
2019年 | 16篇 |
2018年 | 19篇 |
2017年 | 14篇 |
2016年 | 17篇 |
2015年 | 33篇 |
2014年 | 31篇 |
2013年 | 42篇 |
2012年 | 50篇 |
2011年 | 38篇 |
2010年 | 28篇 |
2009年 | 21篇 |
2008年 | 24篇 |
2007年 | 16篇 |
2006年 | 17篇 |
2005年 | 17篇 |
2004年 | 17篇 |
2003年 | 19篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1964年 | 2篇 |
1963年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有517条查询结果,搜索用时 15 毫秒
91.
Angelica Crottini Janina Dordel Jrn Khler Frank Glaw Andreas Schmitz Miguel Vences 《Molecular phylogenetics and evolution》2009,53(1):345-350
A phylogeny for 29 species of scincine lizards from Madagascar, based on 3693 bp of six mitochondrial and five nuclear genes, revealed multiple parallel evolution of adaptations for a burrowing life, and unexpected relationships of the monotypic genera Androngo and Cryptoscincus. Androngo trivittatus was sister to Pygomeles braconnieri, and Cryptoscincus minimus was deeply nested within the genus Paracontias, all of these being fossorial taxa of elongated bodies and partly or fully reduced limbs. To account for these results, we place Cryptoscincus as a junior synonym of Paracontias, and discuss possible taxonomic consequences that may affect the status of Androngo, once additional data become available. 相似文献
92.
Ryan Tewhey Masakazu Nakano Xiaoyun Wang Carlos Pabón-Peña Barbara Novak Angelica Giuffre Eric Lin Scott Happe Doug N Roberts Emily M LeProust Eric J Topol Olivier Harismendy Kelly A Frazer 《Genome biology》2009,10(10):1-13
Background
Genome sequences, now available for most pathogens, hold promise for the rational design of new therapies. However, biological resources for genome-scale identification of gene function (notably genes involved in pathogenesis) and/or genes essential for cell viability, which are necessary to achieve this goal, are often sorely lacking. This holds true for Neisseria meningitidis, one of the most feared human bacterial pathogens that causes meningitis and septicemia.Results
By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization.Conclusions
By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies. 相似文献93.
Claudia Kanashiro Tatiana C Santos Angelica Maria Miglino Andrea M Mess Anthony M Carter 《Reproductive biology and endocrinology : RB&E》2009,7(1):57-13
Background
The guinea pig is an attractive model for human pregnancy and placentation, mainly because of its haemomonochorial placental type, but is rather small in size. Therefore, to better understand the impact of body mass, we studied placental development in the capybara which has a body mass around 50 kg and a gestation period of around 150 days. We paid attention to the development of the lobulated arrangement of the placenta, the growth of the labyrinth in the course of gestation, the differentiation of the subplacenta, and the pattern of invasion by extraplacental trophoblast. 相似文献94.
Martin Montes Cesar Sanchez Kristien Verdonck Jordan E. Lake Elsa Gonzalez Giovanni Lopez Angelica Terashima Thomas Nolan Dorothy E. Lewis Eduardo Gotuzzo A. Clinton White Jr 《PLoS neglected tropical diseases》2009,3(6)
Background
Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite.Objective
To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection.Methods
Peripheral blood mononuclear cells (PBMCs) were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production.Results
Patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm3, p = 0.09, Mann-Whitney test). The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA). Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test). Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells.Conclusions
Regulatory T cell counts are increased in patients with HTLV-1 and Strongyloides stercoralis co-infection and correlate with both low circulating eosinophil counts and reduced antigen-driven IL-5 production. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection. 相似文献95.
Heiko Wurdak Shoutian Zhu Angelica Romero Mihaela Lorger James Watson Chih-yuan Chiang Jay Zhang Vanita S. Natu Luke L. Lairson John R. Walker Christopher M. Trussell Griffith R. Harsh Hannes Vogel Brunhilde Felding-Habermann Anthony P. Orth Loren J. Miraglia Daniel R. Rines Stephen L. Skirboll Peter G. Schultz 《Cell Stem Cell》2010,6(1):37-47
96.
Watanabe MA Nunes SO Nunes SO Amarante MK Guembarovski RL Oda JM Lima KW Fungaro MH 《Journal of genetics》2011,90(1):179-185
Data suggest that the serotonin (5-hydroxytryptamine, 5-HT) system is implicated in the pathogenesis of multiple neuropsychiatric
disorders and may also be involved in smoking behaviour since nicotine increases brain serotonin secretion. It is known that
smoking behaviour is influenced by both genetic and environmental factors. The present review examines the role of the serotonin
transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene with smoking.
This study discusses a polymorphism which has been investigated by many researchers, as the bi-allelic insertion/deletion
polymorphism in the 5′- flanking promoter region (5-HTTLPR). This gene has received considerable attention in attempts to understand the molecular
determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter
in smoking behaviour is reviewed considering the interactive effect of genetic factors. 相似文献
97.
Nicholas J Boddicker Angelica Bjorkquist Raymond RR Rowland Joan K Lunney James M Reecy Jack CM Dekkers 《遗传、选种与进化》2014,46(1):18
Background
Host genetics has been shown to play a role in porcine reproductive and respiratory syndrome (PRRS), which is the most economically important disease in the swine industry. A region on Sus scrofa chromosome (SSC) 4 has been previously reported to have a strong association with serum viremia and weight gain in pigs experimentally infected with the PRRS virus (PRRSV). The objective here was to identify haplotypes associated with the favorable phenotype, investigate additional genomic regions associated with host response to PRRSV, and to determine the predictive ability of genomic estimated breeding values (GEBV) based on the SSC4 region and based on the rest of the genome. Phenotypic data and 60 K SNP genotypes from eight trials of ~200 pigs from different commercial crosses were used to address these objectives.Results
Across the eight trials, heritability estimates were 0.44 and 0.29 for viral load (VL, area under the curve of log-transformed serum viremia from 0 to 21 days post infection) and weight gain to 42 days post infection (WG), respectively. Genomic regions associated with VL were identified on chromosomes 4, X, and 1. Genomic regions associated with WG were identified on chromosomes 4, 5, and 7. Apart from the SSC4 region, the regions associated with these two traits each explained less than 3% of the genetic variance. Due to the strong linkage disequilibrium in the SSC4 region, only 19 unique haplotypes were identified across all populations, of which four were associated with the favorable phenotype. Through cross-validation, accuracies of EBV based on the SSC4 region were high (0.55), while the rest of the genome had little predictive ability across populations (0.09).Conclusions
Traits associated with response to PRRSV infection in growing pigs are largely controlled by genomic regions with relatively small effects, with the exception of SSC4. Accuracies of EBV based on the SSC4 region were high compared to the rest of the genome. These results show that selection for the SSC4 region could potentially reduce the effects of PRRS in growing pigs, ultimately reducing the economic impact of this disease. 相似文献98.
99.
Andrew A. Sproul Samson Jacob Deborah Pre Soong Ho Kim Michael W. Nestor Miriam Navarro-Sobrino Ismael Santa-Maria Matthew Zimmer Soline Aubry John W. Steele David J. Kahler Alex Dranovsky Ottavio Arancio John F. Crary Sam Gandy Scott A. Noggle 《PloS one》2014,9(1)
Presenilin 1 (PSEN1) encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer''s disease (FAD). In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs) derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs) from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes. 相似文献
100.
Samuel G. Penny Franco Andreone Angelica Crottini Marc W. Holderied Lovasoa Sylviane Rakotozafy Christoph Schwitzer Gon?alo M. Rosa 《ZooKeys》2014,(435):111-132
A new species of treefrog of the Boophis rappiodes group (Anura, Mantellidae) is described from the Sahamalaza – Iles Radama National Park in northwest Madagascar. This new species is green in colour with bright red speckling across its head and dorsum; similar in morphology to other species of this group including: B. bottae, B. rappiodes, B. erythrodactylus and B. tasymena. The new species can be distinguished by its advertisement call and by a genetic divergence of more than 4.9% in the analysed mitochondrial 16S rRNA gene fragment. Its call consists of two note types: a trill and a click; although similar sounding to B. bottae, the trill note of the new species has a faster pulse rate while the click note is predominantly two-pulsed rather than three. All individuals were detected from the banks of two streams in Ankarafa Forest. The new species represents the only member of the B. rappiodes group endemic to Madagascar’s western coast, with the majority of other members known from the eastern rainforest belt. Despite its conspicuous call, it has not been detected from other surveys of northwest Madagascar and it is likely to be a local endemic to the peninsula. The ranges of two other amphibian species also appear restricted to Sahamalaza, and so the area seems to support a high level of endemicity. Although occurring inside a National Park, this species is highly threatened by the continuing decline in the quality and extent of its habitat. Due to these threats it is proposed that this species should be classified as Critically Endangered according to the IUCN Red List criteria. 相似文献