全文获取类型
收费全文 | 7891篇 |
免费 | 628篇 |
国内免费 | 1篇 |
出版年
2023年 | 74篇 |
2022年 | 122篇 |
2021年 | 263篇 |
2020年 | 220篇 |
2019年 | 217篇 |
2018年 | 327篇 |
2017年 | 242篇 |
2016年 | 381篇 |
2015年 | 451篇 |
2014年 | 487篇 |
2013年 | 561篇 |
2012年 | 664篇 |
2011年 | 612篇 |
2010年 | 381篇 |
2009年 | 336篇 |
2008年 | 409篇 |
2007年 | 402篇 |
2006年 | 375篇 |
2005年 | 238篇 |
2004年 | 244篇 |
2003年 | 216篇 |
2002年 | 186篇 |
2001年 | 152篇 |
2000年 | 150篇 |
1999年 | 122篇 |
1998年 | 61篇 |
1997年 | 56篇 |
1996年 | 48篇 |
1995年 | 36篇 |
1994年 | 37篇 |
1993年 | 33篇 |
1992年 | 52篇 |
1991年 | 37篇 |
1990年 | 19篇 |
1989年 | 48篇 |
1988年 | 22篇 |
1987年 | 21篇 |
1986年 | 10篇 |
1985年 | 20篇 |
1984年 | 28篇 |
1983年 | 23篇 |
1982年 | 19篇 |
1981年 | 9篇 |
1979年 | 9篇 |
1978年 | 13篇 |
1975年 | 8篇 |
1974年 | 12篇 |
1971年 | 10篇 |
1970年 | 6篇 |
1968年 | 7篇 |
排序方式: 共有8520条查询结果,搜索用时 125 毫秒
961.
Luciana Gabriel Nogueira Ronaldo Honorato Barros Santos Barbara Maria Ianni Alfredo Inácio Fiorelli Eliane Conti Mairena Luiz Alberto Benvenuti Amanda Frade Eduardo Donadi Fabrício Dias Bruno Saba Hui-Tzu Lin Wang Abilio Fragata Marcelo Sampaio Mario Hiroyuki Hirata Paula Buck Charles Mady Edimar Alcides Bocchi Noedir Antonio Stolf Jorge Kalil Edecio Cunha-Neto 《PLoS neglected tropical diseases》2012,6(10)
Background
Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium.Methods and Results
Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes.Conclusions
Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC. 相似文献962.
O. Akinbo M. T. Labuschagne J. Marín C. Ospina L. Santos E. Barrera J. Gutiérrez F. Ewa E. Okogbenin M. Fregene 《Tropical plant biology》2012,5(2):161-172
Root protein content of elite cassava is very low, largely due to breeder’s selection for other agronomic traits mainly fresh
weight yield and disease resistance. Increased protein content in the root of cassava will improve its usefulness as a more
complete food source in the developing world. An inter-specific F1 hybrid CW 198 - 11 was earlier developed at International Center for Tropical Agriculture (CIAT), Cali, Colombia by genetic
crosses of OW 230 - 1 (FLA 441 - 5) and CW 30–65 (an inter-specific hybrid between an improved cassava variety SG 427 - 87
and an accession of Manihot esculenta ssp flabellifolia (MESCFLAX – 80)). The inter-specific cross was ‘backcrossed’, in the sense of another cross to cassava (MTAI – 8) to generate
a B1P2 family with 225 progenies in which major quantitative trait loci (QTL) for root protein in the backcross population of cassava
were identified. A linkage map from the female parent of the backcross population was used for QTL detection. A total of three
QTL (protg.7, protg.13 and protg.23) controlling protein were identified in three different environments. One QTL was expressed across all three environments.
These results demonstrated high broad sense heritability of 61.6% for protein over 2 years, in two different locations. The
individual effects of alleles at these QTL explained from 15% to 25% of the phenotypic variance. The consistency of QTL controlling
protein across environments reveals their potential for use in marker-assisted recurrent selection. 相似文献
963.
Letícia Helena dos Santos Marques Luciana Inácia Gomes Iara Caixeta Marques da Rocha Thaís Almeida Marques da Silva Edward Oliveira Maria Helena Franco Morais Ana Rabello Mariangela Carneiro 《PLoS neglected tropical diseases》2012,6(12)
Background
An important issue associated with the control of visceral leishmaniasis is the need to identify and understand the relevance of asymptomatic infection caused by Leishmania infantum. The aim of this study was to follow the course of asymptomatic L. infantum infection in children in an area of Brazil where it is endemic. The children were assessed twice during a 12-month period.Methodology
In this population study, 1875 children, ranging from 6 months to 7 years of age, were assessed. Blood samples were collected on filter papers via finger prick and tested by ELISA (L. infantum soluble antigen and rk39). Seropositives samples (n = 317) and a number of seronegatives samples (n = 242) were subjected to qPCR. After 12 months, blood samples were collected from a subgroup of 199 children and tested for Leishmania spp. to follow the course of infection.Principal Findings
At baseline qPCR testing identified 82 positive samples. The prevalence rate, as estimated for 1875 children based on the qPCR results, was 13.9%. The qPCR testing of whole blood samples collected from a cohort of children after 12 months (n = 199) yielded the following results: of the 44 (22.1%) children with positive qPCR results at baseline, only 10 (5.0%) remained positive, and 34 (17.1%) became negative; and of the 155 (77.9%) children with negative qPCR results, 131 (65.8%) remained negative, and 24 (12.1%) became positive at the follow-up measurement. The samples with positive findings at baseline (n = 82) had a mean of 56.5 parasites/mL of blood; and at follow-up the mean positive result was 7.8 parasites/mL.Conclusions
The peripheral blood of asymptomatic children had a low and fluctuating quantity of Leishmania DNA and a significant decrease in parasitemia at 1-year follow-up. Quantitative PCR enables adequate monitoring of Leishmania infection. 相似文献964.
Lívia Almeida Uehara Otacílio C. Moreira Ana Carolina Oliveira Patrícia Azambuja Ana Paula Cabral Araujo Lima Constan?a Britto André Luis Souza dos Santos Marta Helena Branquinha Claudia Masini d'Avila-Levy 《PLoS neglected tropical diseases》2012,6(12)
Background
Trypanosoma cruzi is the etiological agent of Chagas'' disease. Cysteine peptidases are relevant to several aspects of the T. cruzi life cycle and are implicated in parasite-mammalian host relationships. However, little is known about the factors that contribute to the parasite-insect host interaction.Methodology/Principal Findings
Here, we have investigated whether cruzipain could be involved in the interaction of T. cruzi with the invertebrate host. We analyzed the effect of treatment of T. cruzi epimastigotes with anti-cruzipain antibodies or with a panel of cysteine peptidase inhibitors (cystatin, antipain, E-64, leupeptin, iodocetamide or CA-074-OMe) on parasite adhesion to Rhodnius prolixus posterior midgut ex vivo. All treatments, with the exception of CA074-OMe, significantly decreased parasite adhesion to R. prolixus midgut. Cystatin presented a dose-dependent reduction on the adhesion. Comparison of the adhesion rate among several T. cruzi isolates revealed that the G isolate, which naturally possesses low levels of active cruzipain, adhered to a lesser extent in comparison to Dm28c, Y and CL Brener isolates. Transgenic epimastigotes overexpressing an endogenous cruzipain inhibitor (pCHAG), chagasin, and that have reduced levels of active cruzipain adhered to the insect gut 73% less than the wild-type parasites. The adhesion of pCHAG parasites was partially restored by the addition of exogenous cruzipain. In vivo colonization experiments revealed low levels of pCHAG parasites in comparison to wild-type. Parasites isolated after passage in the insect presented a drastic enhancement in the expression of surface cruzipain.Conclusions/Significance
These data highlight, for the first time, that cruzipain contributes to the interaction of T. cruzi with the insect host. 相似文献965.
966.
Rafael Barros de Souza Billy Manoel dos Santos Raquel de Fátima Rodrigues de Souza Paula Katharina Nogueira da Silva Brígida Thais Luckwu Lucena Marcos Antonio de Morais Jr. 《Journal of industrial microbiology & biotechnology》2012,39(11):1645-1650
This work describes the effects of the presence of the yeast Dekkera bruxellensis and the bacterium Lactobacillus vini on the industrial production of ethanol from sugarcane fermentation. Both contaminants were quantified in industrial samples, and their presence was correlated to a decrease in ethanol concentration and accumulation of sugar. Then, laboratory mixed-cell fermentations were carried out to evaluate the effects of these presumed contaminants on the viability of Saccharomyces cerevisiae and the overall ethanol yield. The results showed that high residual sugar seemed the most significant factor arising from the presence of D. bruxellensis in the industrial process when compared to pure S. cerevisiae cultures. Moreover, when L. vini was added to S. cerevisiae cultures it did not appear to affect the yeast cells by any kind of antagonistic effect under stable fermentations. In addition, when L. vini was added to D. bruxellensis cultures, it showed signs of being able to stimulate the fermentative activity of the yeast cells in a way that led to an increase in the ethanol yield. 相似文献
967.
Vdo C Souza KB Schlemmer CB Noal JA Jaques CE Zimmermann CA Leal J Fleck EA Casali VM Morsch MR Schetinger DB Leal 《Parasitology international》2012,61(4):690-696
Trypanosoma cruzi infection triggers a chronic inflammatory process in human host and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune responses. In this study, it was investigated ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase; EC 3.6.1.5; CD39) and ecto-adenosine deaminase (E-ADA; EC 3.5.4.4) activities in lymphocytes from patients with indeterminate form of Chagas' disease (IFCD). Twenty-five IFCD patients and 25 healthy subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Adenine nucleotides and adenosine levels were determined in serum by HPLC and the E-NTPDase1 expression in lymphocytes by Western blot analysis. E-NTPDase (ATP and ADP as substrates) and E-ADA (adenosine as substrate) activities were decreased in lymphocytes from IFCD patients (P<0.05 and P<0.01, respectively), while the E-NTPDase1 expression presented no changes in these patients. Serum ATP levels showed to be decreased (P<0.05) and both AMP (P<0.01) and adenosine (P<0.001) levels were increased in the IFCD group. The enzymatic alterations observed are in agreement with the immune response against T. cruzi infection in IFCD patients, since the decreased extracellular ATP and the increased adenosine levels trigger a Th2 anti-inflammatory response, which it is associated to adaptation of host to parasite, preventing clinical progress of disease. 相似文献
968.
de Farias JD Santos MG de França AK Delani D Tada MS Casseb AA Simões AL Engracia V 《Genetics and molecular biology》2012,35(1):27-31
Since around 1723, on the occasion of its initial colonization by Europeans, Rondonia has received successive waves of immigrants. This has been further swelled by individuals from northeastern Brazil, who began entering at the beginning of the twentieth century. The ethnic composition varies across the state according to the various sites of settlement of each wave of immigrants. We analyzed the frequency of the CCR5Δ32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in five sample sets from the population. Four were collected in Porto Velho, the state capital and the site of several waves of migration. Of these, two, from the Hospital de Base were comprised of HB Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%, respectively, a third from the peri-urban neighborhoods of Candelária/Bate-Estaca (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%) came from the inland Quilombola village of Pedras Negras. Two homozygous individuals (CCR5Δ32/CCR5Δ32) were detected among the HB Mother samples. The frequency of this allele was heterogeneous and higher where the European inflow was more pronounced. The presence of the allele in Pedras Negras revealed European miscegenation in a community largely comprising Quilombolas. 相似文献
969.
da Costa da Santos EK Honda RT Nozawa SR Ferreira-Nozawa MS 《Genetics and molecular biology》2012,35(1):134-141
Analysis of bacterial diversity in soils along the banks of the Solimões and
Negro rivers, state of Amazonas, Brazil, was by partial sequencing of the genes codifying
the rDNA16S region. Diversity of operational taxonomic units (OTU) and of the divergent
sequences obtained were applied in comparative analysis of microbiological diversity in
the two environments, based on richness estimators and OTU diversity indices. The higher
OTU diversity in the Solimões was based on the higher number of parameters that
evoke this. The interaction between the nucleotide sequences of bacteria inhabiting the
two riverine environments indicated that the two microrganism communities are similar in
composition. 相似文献
970.
Amador RR Longo JP Lacava ZG Dórea JG Almeida Santos Mde F 《Genetics and molecular biology》2012,35(1):153-158
Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays) and in mice (micronucleus assays). Concentrations of 114.4 μg/mL and 572 μg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 μg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage. 相似文献