全文获取类型
收费全文 | 576篇 |
免费 | 26篇 |
出版年
2023年 | 6篇 |
2022年 | 10篇 |
2021年 | 19篇 |
2020年 | 18篇 |
2019年 | 37篇 |
2018年 | 11篇 |
2017年 | 24篇 |
2016年 | 30篇 |
2015年 | 23篇 |
2014年 | 31篇 |
2013年 | 48篇 |
2012年 | 48篇 |
2011年 | 43篇 |
2010年 | 26篇 |
2009年 | 14篇 |
2008年 | 28篇 |
2007年 | 17篇 |
2006年 | 28篇 |
2005年 | 16篇 |
2004年 | 17篇 |
2003年 | 22篇 |
2002年 | 11篇 |
2001年 | 14篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有602条查询结果,搜索用时 483 毫秒
51.
Poornima Parameswaran Ella Sklan Courtney Wilkins Trever Burgon Melanie A. Samuel Rui Lu K. Mark Ansel Vigo Heissmeyer Shirit Einav William Jackson Tammy Doukas Suman Paranjape Charlotta Polacek Flavia Barreto dos Santos Roxana Jalili Farbod Babrzadeh Baback Gharizadeh Dirk Grimm Mark Kay Satoshi Koike Peter Sarnow Mostafa Ronaghi Shou-Wei Ding Eva Harris Marie Chow Michael S. Diamond Karla Kirkegaard Jeffrey S. Glenn Andrew Z. Fire 《PLoS pathogens》2010,6(2)
We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts. 相似文献
52.
Bueris V Sircili MP Taddei CR dos Santos MF Franzolin MR Martinez MB Ferrer SR Barreto ML Trabulsi LR 《Memórias do Instituto Oswaldo Cruz》2007,102(7):839-844
We identified different diarrheagenic (DEC) Escherichia coli pathotypes isolated from 1,207 children with and without acute endemic diarrhea in Salvador, Bahia, Brazil collected as part of a case-control study. Since the identification of DEC cannot be based on only biochemical and culture criteria, we used a multiplex polymerase chain reaction developed by combining five specific primer pairs for Enteropathogenic Escherichia coli (EPEC), Shiga toxin-producing E. coli/ Enterohaemorrhagic E. coli (STEC/EHEC), Enterotoxigenic E. coli (ETEC) and Enteroaggregative E. coli (EAEC) to detect these pathotypes simultaneously in a single-step reaction. In order to distinguish typical and atypical EPEC strains, these were tested for the presence of EAF plasmid. The prevalence of diarrheagenic E. coli in this sample of a global case-control study was 25.4% (259 patients) and 18.7% (35 patients) in the diarrhea group (1,020 patients) and the control group (187 patients), respectively. The most frequently isolated pathotype was EAEC (10.7%), followed by atypical EPEC (9.4%), ETEC (3.7%), and STEC (0.6%). Typical EPEC was detected only in one sample. The prevalence of the pathotypes studied in children with diarrhea was not significantly different from that in children without diarrhea. 相似文献
53.
Thyroid Hormones Reorganize the Cytoskeleton of Glial Cells Through Gfap Phosphorylation and Rhoa-Dependent Mechanisms 总被引:1,自引:0,他引:1
Zamoner A Funchal C Jacques-Silva MC Gottfried C Barreto Silva FR Pessoa-Pureur R 《Cellular and molecular neurobiology》2007,27(7):845-865
Thyroid hormones (3,5,3′-triiodo-l-thyronine, T3; 3,5,3′,5′-l-tetraiodothyronine, T4; TH) play crucial roles in the growth and differentiation of the central nervous system. In this study, we investigated the
actions of TH on proliferation, viability, cell morphology, in vitro phosphorylation of glial fibrillary acidic protein (GFAP)
and actin reorganization in C6 glioma cells. We first observe that long-term exposure to TH stimulates cell proliferation
without induce cell death. We also demonstrate that after 3, 6, 12, 18, and 24 h treatment with TH, C6 cells and cortical
astrocytes show a process-bearing shape. Furthermore, immunocytochemistry with anti-actin and anti-GFAP antibodies reveals
that TH induces reorganization of actin and GFAP cytoskeleton. We also observe an increased in vitro 32P incorporation into GFAP recovered into the high-salt Triton insoluble cytoskeletal fraction after 3 and 24 h exposure to
5×10−8 and 10−6 M T3, and only after 24 h exposure to 10−9 M T4. These results show a T3 action on the phosphorylating system associated to GFAP and suggest a T3-independent effect of T4 on this cytoskeletal protein. In addition, C6 cells and astrocytes treated with lysophosphatidic acid, an upstream activator
of the RhoA GTPase pathway, totally prevented the morphological alterations induced by TH, indicating that this effect could
be mediated by the RhoA signaling pathway. Considering that IF network can be regulated by phosphorylation leading to reorganization
of IF filamentous structure and that alterations of the microfilament organization may have important implications in glial
functions, the effects of TH on glial cell cytoskeleton could be implicated in essential neural events such as brain development. 相似文献
54.
de Araújo MV Vieira EK Lázaro GS de Souza Conegero L Ferreira OP Almeida LS Barreto LS da Costa NB Gimenez IF 《Bioorganic & medicinal chemistry》2007,15(17):5752-5759
The inclusion complexation of pyrimethamine in 2-hydroxypropyl-beta-cyclodextrin has been investigated by 2D (1)H NMR, FTIR and UV/visible spectroscopy and also by molecular modelling methods (AM1, PM3, MM3). From the phase-solubility diagram a linear increase was observed in pyrimethamine aqueous solubility in the presence of 2-hydroxypropyl-beta-cyclodextrin, evidencing the formation of a soluble inclusion complex. According to the continuous variation method (Job's plot) applied to fluorescence measurements, a 1:1 stoichiometry has been proposed for the complex. Concerning the structure of the complex, a Cl-in orientation of pyrimethamine in the 2-hydroxypropyl-beta-cyclodextrin cavity has been proposed from the theoretical calculations, being confirmed by two-dimensional (1)H NMR spectroscopy (ROESY). The thermal behaviour has also been studied, providing complementary evidences of complex formation. 相似文献
55.
The keystone species Pisaster ochraceus suffered mass mortalities along the northeast Pacific Ocean from Sea Star Wasting Syndrome (SSWS) outbreaks in 2013–2016. SSWS causation remains of debate, leading to concerns as to whether outbreaks will continue to impact this species. Considering the apparent link between ocean temperature and SSWS, the future of this species and intertidal communities remains uncertain. Surveys of co-occurring apparently normal and wasting P. ochraceus along the central Oregon coast in 2016 allowed us to address whether variation in disease status showed genetic variation that may be associated with differences in susceptibility to SSWS. We performed restriction site-associated DNA sequencing (2bRAD-seq) to genotype ~72,000 single nucleotide polymorphism (SNP) loci across apparently normal and wasting sea stars. Locus-specific analyses of differentiation (FST) between disease-status groups revealed no signal of genetic differences separating the two groups. Using a multivariate approach, we observed weak separation between the groups, but identified 18 SNP loci showing highest discriminatory power between the groups and scanned the genome annotation for linked genes. A total of 34 protein-coding genes were found to be located within 15 kb (measured by linkage disequilibrium decay) of at least one of the 18 SNPs, and 30 of these genes had homologies to annotated protein databases. Our results suggest that the likelihood of developing SSWS symptoms does not have a strong genetic basis. The few genomic regions highlighted had only modest levels of differentiation, but the genes associated with these regions may form the basis for functional studies aiming to understand disease progression. 相似文献
56.
Joel Vega‐Rodriguez Davinia Perez‐Barreto Antonio Ruiz‐Reyes Marcelo Jacobs‐Lorena 《Cellular microbiology》2015,17(11):1594-1604
Malaria remains one of the most devastating infectious diseases, killing up to a million people every year. Whereas much progress has been made in understanding the life cycle of the parasite in the human host and in the mosquito vector, significant gaps of knowledge remain. Fertilization of malaria parasites, a process that takes place in the lumen of the mosquito midgut, is poorly understood and the molecular interactions (receptor–ligand) required for Plasmodium fertilization remain elusive. By use of a phage display library, we identified FG1 (Female Gamete peptide 1), a peptide that binds specifically to the surface of female Plasmodium berghei gametes. Importantly, FG1 but not a scrambled version of the peptide, strongly reduces P. berghei oocyst formation by interfering with fertilization. In addition, FG1 also inhibits P. falciparum oocyst formation suggesting that the peptide binds to a molecule on the surface of the female gamete whose structure is conserved. Identification of the molecular interactions disrupted by the FG1 peptide may lead to the development of novel malaria transmission‐blocking strategies. 相似文献
57.
58.
Jerônimo Boelsums Barreto Sansevero Pablo Viany Prieto Luiz Fernando Duarte de Moraes Pablo JoséFrancisco Pena Rodrigues 《Restoration Ecology》2011,19(3):379-389
Plantations of native‐tree species are often recommended for ecological restoration, but the understanding of how these techniques catalyze natural ecological processes is limited. We investigated natural regeneration in five plantations of native trees in the Poço das Antas Biological Reserve (PABR) in the state of Rio de Janeiro, Brazil. The plantations were 9–11 years old, and contained 8–14 native‐tree species with different compositions and relative density of species. We analyzed floristic composition, structure (density and basal area) of overstory and understory strata, as well as other ecological attributes (dispersal syndromes, fruit or seed size, and the availability of fruit for frugivores). Zoochorous species comprised 77% of the community, with a prevalence of the two smallest size classes of propagules (< 0.6 and 0.6–1.6 cm) in natural regeneration. The density of zoochorous plants in the understory was positively correlated with their density in the overstory, indicating their influence on natural regeneration (r2 = 0.36; p < 0.0002). Fruit availability for frugivores (density and richness of plants fruiting during the year) was also positively correlated with the density of stems in the understory. Therefore, attributes such as dispersal syndrome and fruiting season should be considered in selecting species to be planted. The differences in natural regeneration observed in each of the native‐tree plantations indicated that the performance of plantations as a restoration strategy may differ, depending on initial species composition, planting density, and site conditions. 相似文献
59.
Lima Mda R Nogueira RM Schatzmayr HG de Filippis AM Limonta D dos Santos FB 《PLoS neglected tropical diseases》2011,5(5):e1147
Abstract/Background
Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23) that occurred in 2002 in Brazil.Methodology/Principal Findings
A total of 74 tissue specimens were available: liver (n = 23), lung (n = 14), kidney (n = 04), brain (n = 10), heart (n = 02), skin (n = 01), spleen (n = 15), thymus (n = 03) and lymph nodes (n = 02). We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 Ag Strip (BioRad Laboratories). The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23), 60.8% (14/23) and 91.3% (21/23), respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74) of the specimens analyzed and the Platelia NS1 in 45.9% (34/74). The highest sensitivity (78.3%; 58/74) was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05). The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23), lung (71.4%; 10/14), kidney (100%; 4/4), brain (80%; 8/10), spleen (66.6%, 10/15) and thymus (100%, 3/3) when compared to the other two ELISA assays.Conclusions/Significance
This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an increasing number of DHF and fatal cases, the availability of new approaches useful for cases confirmation plays an important tool for the disease surveillance. 相似文献60.