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961.
Christine Danel Mathieu Kabran André Inwoley Anani Badje Jean Louis Herrmann Raoul Moh Jér?me Lecarrou Delphine Gabillard Jean Baptiste Ntakpe Nina Deschamps Eric Ouattara Christian Perronne Serge Eholie Xavier Anglaret 《PloS one》2014,9(10)
Objective
To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT).Methods
Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml.Results
Among the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion.Conclusion
A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases.Trial Registration
ClinicalTrials.gov . NCT00495651相似文献962.
Adriana Farias Silva Erick Leite Bastos Marcelo Der Torossian Torres André Luis Costa‐da‐Silva Rafaella Sayuri Ioshino Margareth Lara Capurro Flávio Lopes Alves Antonio Miranda Renata de Freitas Fischer Vieira Vani Xavier Oliveira Jr. 《Journal of peptide science》2014,20(8):640-648
Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid‐phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide‐capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. The Ala screening data indicates that the replacement of either the Ile5 or the His6 residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala6]‐AII (79%), and [Ala5]‐AII (75%). Analogs [Ala3]‐AII, [Ala1]‐AII, and AII‐NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala8]‐AII, [Ala7]‐AII, [Ala4]‐AII, and [Ala2]‐AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a β‐fold conformation in different solutions. All AII analogs, except [Ala4]‐AII and [Ala8]‐AII, show contractile responses and interact with the AT1 receptor, [Ala5]‐AII and [Ala6]‐AII. In conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
963.
Micka?l Bouvet Adrien Lugari Clara C. Posthuma Jessika C. Zevenhoven Stéphanie Bernard Stéphane Betzi Isabelle Imbert Bruno Canard Jean-Claude Guillemot Patrick Lécine Susanne Pfefferle Christian Drosten Eric J. Snijder Etienne Decroly Xavier Morelli 《The Journal of biological chemistry》2014,289(37):25783-25796
The RNA-synthesizing machinery of the severe acute respiratory syndrome Coronavirus (SARS-CoV) is composed of 16 non-structural proteins (nsp1–16) encoded by ORF1a/1b. The 148-amino acid nsp10 subunit contains two zinc fingers and is known to interact with both nsp14 and nsp16, stimulating their respective 3′-5′ exoribonuclease and 2′-O-methyltransferase activities. Using alanine-scanning mutagenesis, in cellulo bioluminescence resonance energy transfer experiments, and in vitro pulldown assays, we have now identified the key residues on the nsp10 surface that interact with nsp14. The functional consequences of mutations introduced at these positions were first evaluated biochemically by monitoring nsp14 exoribonuclease activity. Disruption of the nsp10-nsp14 interaction abrogated the nsp10-driven activation of the nsp14 exoribonuclease. We further showed that the nsp10 surface interacting with nsp14 overlaps with the surface involved in the nsp10-mediated activation of nsp16 2′-O-methyltransferase activity, suggesting that nsp10 is a major regulator of SARS-CoV replicase function. In line with this notion, reverse genetics experiments supported an essential role of the nsp10 surface that interacts with nsp14 in SARS-CoV replication, as several mutations that abolished the interaction in vitro yielded a replication-negative viral phenotype. In contrast, mutants in which the nsp10-nsp16 interaction was disturbed proved to be crippled but viable. These experiments imply that the nsp10 surface that interacts with nsp14 and nsp16 and possibly other subunits of the viral replication complex may be a target for the development of antiviral compounds against pathogenic coronaviruses. 相似文献
964.
965.
Wenjing Zhang Yaoyu E. Wang Yu Zhang Xavier Leleu Michaela Reagan Yong Zhang Yuji Mishima Siobhan Glavey Salomon Manier Antonio Sacco Bo Jiang Aldo M. Roccaro Irene M. Ghobrial 《PloS one》2014,9(10)
Epigenetic changes frequently occur during tumorigenesis and DNA hypermethylation may account for the inactivation of tumor suppressor genes in cancer cells. Studies in Multiple Myeloma (MM) have shown variable DNA methylation patterns with focal hypermethylation changes in clinically aggressive subtypes. We studied global methylation patterns in patients with relapsed/refractory MM and found that the majority of methylation peaks were located in the intronic and intragenic regions in MM samples. Therefore, we investigated the effect of methylation on miRNA regulation in MM. To date, the mechanism by which global miRNA suppression occurs in MM has not been fully described. In this study, we report hypermethylation of miRNAs in MM and perform confirmation in MM cell lines using bisulfite sequencing and methylation-specific PCR (MSP) in the presence or absence of the DNA demethylating agent 5-aza-2′-deoxycytidine. We further characterized the hypermethylation-dependent inhibition of miR-152, -10b-5p and -34c-3p which was shown to exert a putative tumor suppressive role in MM. These findings were corroborated by the demonstration that the same miRNAs were down-regulated in MM patients compared to healthy individuals, alongside enrichment of miR-152-, -10b-5p, and miR-34c-3p-predicted targets, as shown at the mRNA level in primary MM cells. Demethylation or gain of function studies of these specific miRNAs led to induction of apoptosis and inhibition of proliferation as well as down-regulation of putative oncogene targets of these miRNAs such as DNMT1, E2F3, BTRC and MYCBP. These findings provide the rationale for epigenetic therapeutic approaches in subgroups of MM. 相似文献
966.
Samanta Cristina das Chagas Xavier André Luiz Rodrigues Roque Daniele Bilac Vitor Ant?nio Louzada de Araújo Sócrates Fraga da Costa Neto Elias Seixas Lorosa Luiz Felipe Coutinho Ferreira da Silva Ana Maria Jansen 《PLoS neglected tropical diseases》2014,8(5)
Background
The new epidemiological scenario of orally transmitted Chagas disease that has emerged in Brazil, and mainly in the Amazon region, needs to be addressed with a new and systematic focus. Belém, the capital of Pará state, reports the highest number of acute Chagas disease (ACD) cases associated with the consumption of açaí juice.Methodology/Principal Findings
The wild and domestic enzootic transmission cycles of Trypanosoma cruzi were evaluated in the two locations (Jurunas and Val-de Cães) that report the majority of the autochthonous cases of ACD in Belém city. Moreover, we evaluated the enzootic cycle on the three islands that provide most of the açaí fruit that is consumed in these localities. We employed parasitological and serological tests throughout to evaluate infectivity competence and exposure to T. cruzi. In Val-de-Cães, no wild mammal presented positive parasitological tests, and 56% seroprevalence was observed, with low serological titers. Three of 14 triatomines were found to be infected (TcI). This unexpected epidemiological picture does not explain the high number of autochthonous ACD cases. In Jurunas, the cases of ACD could not be autochthonous because of the absence of any enzootic cycle of T. cruzi. In contrast, in the 3 island areas from which the açaí fruit originates, 66.7% of wild mammals and two dogs displayed positive hemocultures, and 15.6% of triatomines were found to be infected by T. cruzi. Genotyping by mini-exon gene and PCR-RFLP (1f8/Akw21I) targeting revealed that the mammals and triatomines from the islands harbored TcI and Trypanosoma rangeli in single and mixed infections.Conclusion/Significance
These findings show that cases of Chagas disease in the urban area of Belém may be derived from infected triatomines coming together with the açaí fruits from distant islands. We term this new epidemiological feature of Chagas disease as “Distantiae transmission”. 相似文献967.
Valdirene dos Santos Lima Samanta Cristina das Chagas Xavier Irene Fabíola Roman Maldonado André Luiz Rodrigues Roque Ana Carolina Paulo Vicente Ana Maria Jansen 《PloS one》2014,9(12)
Trypanosoma cruzi infection is a complex sylvatic enzooty involving a wide range of animal species. Six discrete typing units (DTUs) of T. cruzi, named TcI to TcVI, are currently recognized. One unanswered question concerning the epidemiology of T. cruzi is the distribution pattern of TcII and hybrid DTUs in nature, including their virtual absence in the Brazilian Amazon, the current endemic area of Chagas disease in Brazil. Herein, we characterized biological samples that were collected in previous epizootiological studies carried out in the Amazon Basin in Brazil. We performed T. cruzi genotyping using four polymorphic genes to identify T. cruzi DTUs: mini-exon, 1f8, histone 3 and gp72. This analysis was conducted in the following biological samples: (i) two T. cruzi isolates obtained by culturing of stools from the triatomine species Rhodnius picttipes and (ii) five serum samples from dogs in which trypomastigotes were observed during fresh blood examination. We report for the first time the presence of TcII and hybrid DTUs (TcV/TcVI) in the Amazon region in mixed infections with TcI. Furthermore, sequencing of the constitutive gene, gp72, demonstrated diversity in TcII even within the same forest fragment. These data show that TcII is distributed in the five main Brazilian biomes and is likely more prevalent than currently described. It is very probable that there is no biological or ecological barrier to the transmission and establishment of any DTU in any biome in Brazil. 相似文献
968.
Marta Ollé-Monge Xavier Mu?oz Jeroen A. J. Vanoirbeek Susana Gómez-Ollés Ferran Morell María-Jesus Cruz 《PloS one》2014,9(10)
Introduction
Since persulfate salts are an important cause of occupational asthma (OA), we aimed to study the persistence of respiratory symptoms after a single exposure to ammonium persulfate (AP) in AP-sensitized mice.Material and Methods
BALB/c mice received dermal applications of AP or dimethylsulfoxide (DMSO) on days 1 and 8. On day 15, they received a single nasal instillation of AP or saline. Airway hyperresponsiveness (AHR) was assessed using methacholine provocation, while pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL), and total serum immunoglobulin E (IgE), IgG1 and IgG2a were measured in blood at 1, 4, 8, 24 hours and 4, 8, 15 days after the single exposure to the causal agent. Histological studies of lungs were assessed.Results
AP-treated mice showed a sustained increase in AHR, lasting up to 4 days after the challenge. There was a significant increase in the percentage of neutrophils 8 hours after the challenge, which persisted for 24 hours in AP-treated mice. The extent of airway inflammation was also seen in the histological analysis of the lungs from challenged mice. Slight increases in total serum IgE 4 days after the challenge were found, while IgG gradually increased further 4 to 15 days after the AP challenge in AP-sensitized mice.Conclusions
In AP-sensitized mice, an Ig-independent response is induced after AP challenge. AHR appears immediately, but airway neutrophil inflammation appears later. This response decreases in time; at early stages only respiratory and inflammatory responses decrease, but later on immunological response decreases as well. 相似文献969.
Models have shown that population cycles might be driven by time lags resulting from positive feedback between kin structure and population change, coupled with negative feedback between density and population change. One such model operates through kin favouritism facilitating the recruitment of young cock red grouse. We investigated whether recruitment by young cocks depended on the presence and spatial arrangement of elder relatives in the territorial population. We used molecular genetic estimates of relatedness, and checked for effects of covariates including natal territory size, hatching date, body size, parasite burdens and local density. Philopatric recruitment by cock red grouse led to the formation of clusters of contiguous territories owned by kin. The probability that an individual young cock would establish a territory increased with the number of kin in his father's cluster. This pattern might have been due to genetic quality determining both recruitment success and the size of the paternal cluster. If so, there should have been a positive correlation between a young cock's probability of recruitment and the number of his relatives in the population, irrespective of their spatial distribution. This did not occur and so the effect of cluster size is unlikely to have been confounded by genetic quality. The only morphological measure correlated with recruitment success was supraorbital comb size. The results are consistent with the prediction that kin tolerance affects recruitment but were at the level of the individual within years, rather than the population among years. Hence an experimental test of the kin favouritism hypothesis for population cycles, by manipulation of relatedness in populations among years, is now required. 相似文献
970.
M. Brancourt-Hulmel J. -B. Denis C. Lecomte 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2000,100(2):285-298
Genotype-environment interaction has been analyzed in a winter-wheat breeding network using bi-additive factorial regression
models. This family of models generalizes both factorial regression and biadditive (or AMMI) models; it fits especially well
when abundant external information is available on genotypes and/or environments. Our approach, focused on environmental characterization,
was performed with two kinds of covariates: (1) deviations of yield components measured on four probe genotypes and (2) usual
indicators of yield-limiting factors. The first step was based on the analysis of a crop diagnosis on four probe genotypes.
Difference of kernel number to a threshold number (DKN) and reduction of thousand-kernel weight from a potential value (RTKW)
were used to characterize the grain-number formation and the grain-filling periods, respectively. Grain yield was analyzed
according to a biadditive factorial regression model using eight environmental covariates (DKN and RTKW measured on each of
four probe genotypes). In the second step, the usual indicators of yield-limiting factors were too numerous for the analysis
of grain yield. Thus a selection of a subset of environmental covariates was performed on the analysis of DKN and RTKW for
the four probe genotypes. Biadditive factorial regression models involved environmental covariates related to each deviation
and included environmental main effect, sum of water deficits, an indicator of nitrogen stress, sum of daily radiation, high
temperature, pressure of powdery mildew and lodging. The correlations of each environmental covariate to the synthetic variates
helped to discard those poorly involved in interaction (with | correlation | <0.3). The grain yield of 12 genotypes was interpreted
with the retained covariates using biadditive factorial regression. The models explained about 75% of the interaction sums
of squares. In addition, the biadditive factorial regression biplot gave relevant information about the interaction of the
genotypes (interaction pattern and sensitivities to environmental covariates) with respect to the environmental covariates
and proved to be interesting for such an approach.
Received: 8 March 1999 / Accepted: 29 July 1999 相似文献