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31.
Raquel Soares Maia Godoy Luiza dos Santos Felix Alessandra da Silva Orfan Brbara Aparecida Chaves Paula Monalisa Nogueira Breno dos Anjos Costa Aline Silva Soares Cinthia Catharina Azevedo Oliveira Rafael Nacif-Pimenta Breno Mello Silva Ana Paula Duarte Marcus Vinicius Guimares de Lacerda Wuelton Marcelo Monteiro Ngila Francinete Costa Secundino Paulo Filemon Paolucci Pimenta 《PLoS neglected tropical diseases》2021,15(11)
Dengue virus (DENV) and Zika virus (ZIKV) belong to the same viral family, the Flaviviridae. They cause recurring threats to the public health systems of tropical countries such as Brazil. The primary Brazilian vector of both viruses is the mosquito Aedes aegypti. After the mosquito ingests a blood meal from an infected person, the viruses infect and replicate in the midgut, disseminate to secondary tissues and reach the salivary gland (SG), where they are ready to be transmitted to a vertebrate host. It is thought that the intrinsic discrepancies among mosquitoes could affect their ability to deal with viral infections. This study confirms that the DENV and ZIKV infection patterns of nine Ae. aegypti field populations found in geographically separate health districts of an endemic Brazilian city vary. We analyzed the infection rate, disseminated infection, vector competence, and viral load through quantitative PCR. Mosquitoes were challenged using the membrane-feeding assay technique and were tested seven and fourteen days post-infection (early and late infection phases, respectively). The infection responses varied among the Ae. aegypti populations for both flaviviruses in the two infection phases. There was no similarity between DENV and ZIKV vector competencies or viral loads. According to the results of our study, the risk of viral transmission overtime after infection either increases or remains unaltered in ZIKV infected vectors. However, the risk may increase, decrease, or remain unaltered in DENV-infected vectors depending on the mosquito population. For both flaviviruses, the viral load persisted in the body even until the late infection phase. In contrast to DENV, the ZIKV accumulated in the SG over time in all the mosquito populations. These findings are novel and may help direct the development of control strategies to fight dengue and Zika outbreaks in endemic regions, and provide a warning about the importance of understanding mosquito responses to arboviral infections. 相似文献
32.
ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE 总被引:11,自引:0,他引:11
Wahrle SE Jiang H Parsadanian M Legleiter J Han X Fryer JD Kowalewski T Holtzman DM 《The Journal of biological chemistry》2004,279(39):40987-40993
ABCA1 is an ATP-binding cassette protein that transports cellular cholesterol and phospholipids onto high density lipoproteins (HDL) in plasma. Lack of ABCA1 in humans and mice causes abnormal lipidation and increased catabolism of HDL, resulting in very low plasma apoA-I, apoA-II, and HDL. Herein, we have used Abca1-/- mice to ask whether ABCA1 is involved in lipidation of HDL in the central nervous system (CNS). ApoE is the most abundant CNS apolipoprotein and is present in HDL-like lipoproteins in CSF. We found that Abca1-/- mice have greatly decreased apoE levels in both the cortex (80% reduction) and the CSF (98% reduction). CSF from Abca1-/- mice had significantly reduced cholesterol as well as small apoE-containing lipoproteins, suggesting abnormal lipidation of apoE. Astrocytes, the primary producer of CNS apoE, were cultured from Abca1+/+, +/-, and -/- mice, and nascent lipoprotein particles were collected. Abca1-/- astrocytes secreted lipoprotein particles that had markedly decreased cholesterol and apoE and had smaller apoE-containing particles than particles from Abca1+/+ astrocytes. These findings demonstrate that ABCA1 plays a critical role in CNS apoE metabolism. Since apoE isoforms and levels strongly influence Alzheimer's disease pathology and risk, these data suggest that ABCA1 may be a novel therapeutic target. 相似文献
33.
Santos-Silva AP Lisboa PC Pinheiro CR Maia LA Peixoto-Silva N Abreu-Villaça Y Moura EG Oliveira E 《Hormones et métabolisme》2012,44(7):550-554
Previously, we have shown that maternal smoke exposure during lactation, even when pups are not exposed, affects biochemical profiles in the offspring at weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia and lower adrenal catecholamine content. However, the future impact of tobacco exposure is still unknown. As postnatal nicotine exposure causes short- and long-term effects on pups' biochemistry and endocrine profiles, we have now evaluated some endocrine and metabolic parameters of the adult offspring whose mothers were tobacco exposed during lactation. For this, from day 3 to 21 of lactation, rat dams were divided in: 1) SE group, cigarette smoke-exposed (1.7 mg nicotine/cigarettes for 1 h, 4 times/day, daily), without their pups, and 2) C group, exposed to air, in the same conditions. Offspring were killed at 180-days-old. Body weight and food intake were evaluated. Blood, white adipose tissue, adrenal, and liver were collected. All significant data were p<0.05. The adult SE offspring showed no change in body weight, cumulative food intake, serum hormone profile, serum lipid profile, or triglycerides content in liver. However, in adrenal gland, adult SE offspring showed lower catecholamine content ( - 50%) and lower tyrosine hydroxylase protein expression ( - 56%). Despite the hormonal alterations during lactation, tobacco smoke exposure through breast milk only programmed the adrenal medullary function at adulthood and this dysfunction can have consequence on stress response. Thus, an environment free of smoke during lactation period is essential to improve health outcomes in adult offspring. 相似文献
34.
Diogo Gama Caetano Fernanda Heloise Côrtes Gonzalo Bello Sylvia Lopes Maia Teixeira Brenda Hoagland Beatriz Grinsztejn Valdilea Gonçalves Veloso Monick Lindenmeyer Guimarães Mariza Gonçalves Morgado 《Retrovirology》2018,15(1):62
Background
Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n?=?5) and (2) elite controllers (ECs; n?=?6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes.Results
Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were?<?1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (<?1%); all VCs showed a high number of mutations, with significant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure.Conclusions
The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants.35.
Mutel Chris Liao Xun Patouillard Laure Bare Jane Fantke Peter Frischknecht Rolf Hauschild Michael Jolliet Olivier Maia de Souza Danielle Laurent Alexis Pfister Stephan Verones Francesca 《The International Journal of Life Cycle Assessment》2019,24(5):856-865
The International Journal of Life Cycle Assessment - Regionalized life cycle impact assessment (LCIA) has rapidly developed in the past decade, though its widespread application, robustness, and... 相似文献
36.
Kelly G. Aukema Mian Wang Beatriz de Souza Sophie O'Keane Maia Clipsham Lawrence P. Wackett Alptekin Aksan 《Microbial biotechnology》2022,15(9):2391-2400
Engineered materials to improve the shelf-life of desiccated microbial strains are needed for cost-effective bioaugmentation strategies. High temperatures and humidity of legume-growing regions challenge long-term cell stabilization at the desiccated state. A thermostable xeroprotectant core and hydrophobic water vapour barrier shell encapsulation technique was developed to protect desiccated cells from the environment. A trehalose core matrix increased the stability of desiccated Bradyrhizobium by three orders of magnitude over 20 days at 32°C and 50% relative humidity (RH) compared to buffer alone; however, the improvement was not deemed sufficient for a shelf-stable bioproduct. We tested common additives (skim milk, albumin, gelatin and dextran) to increase the glass transition temperature of the desiccated product to provide further stabilization. Albumin increased the glass transition temperature of the trehalose-based core by 40°C and stabilized desiccated Bradyrhizobium for 4 months during storage at high temperature (32°C) and moderate humidity (50% RH) with only 1 log loss of viability. Although the albumin-trehalose core provided exceptional protection against high temperature, it was ineffective at higher humidity conditions (75%). We therefore incorporated a paraffin shell, which protected desiccated cells against 75% RH providing proof of concept that core and shell encapsulation is an effective strategy to stabilize desiccated cells. 相似文献
37.
Rachel S. N. de Pinho Francisco P. da Silva‐Júnior João Paulo C. Bastos Werllen S. Maia Marco Túlio de Mello Veralice M. S. de Bruin 《Chronobiology international》2013,30(5):963-971
Truck drivers are more likely to suffer severe injury and death due to certain truck driving characteristics. Identifying and preventing factors associated with accidents in this population is important to minimize damage and improve road safety. Excessive daytime sleepiness is a major public health problem, leading to impaired cognitive function, reduced alertness, and increased risk of motor vehicle crashes. The aim of this cross‐sectional study was to determine the prevalence and predictors of hypersomnolence (defined as an Epworth Sleepiness Scale score greater than 10) among truck drivers. Three hundred male truck drivers were studied. Quality of sleep was assessed by the Pittsburgh Sleep Quality Index, and the association between demographic, clinical, and occupational data with excessive sleepiness was analyzed. The mean daily sleep duration was 5.6±1.3 h, and poor quality of sleep was found in 46.3% of the individuals. Hypersomnolence was found in 46% of the drivers and was associated with younger age, snoring, and working >10 h without rest. A positive correlation between hypersomnolence and previous accidents was detected (p=0.005). These results show that sleep deprivation and hypersomnolence are frequent among truck drivers. The treatment of sleep‐disordered breathing and the implementation of educational programs, particularly targeting younger drivers and promoting increased awareness of the deleterious effects of sleep loss and work overload, may help to reduce hypersomnolence and accidents among truck drivers. 相似文献
38.
Luiz Claudio Pereira Ribeiro Cassia Cristina Alves Gon?alves Carla Maria Sena Andrade Slater Silvia Maia Farias de Carvalho Marzia Puccioni-Sohler 《Memórias do Instituto Oswaldo Cruz》2013,108(6):730-734
Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies
(Abs) represents conclusive evidence of a specific immune response in the
central nervous system of HTLV-1 associated myelopathy/tropical spastic
paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a
confirmatory test for HTLV-1 infection. The aim of this study was to standardise
the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1
proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples
were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative
patients and two HTLV-1 patients without definite HAM/TSP. The presence of
reactive bands of greater intensity in the CSF compared to serum (or bands in
only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All
definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1
Abs; these Abs were not detected in the control patients. The most frequent
intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a
lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal
immune response against env (GD21 and rgp46-I) and
gag (p24) proteins represents the most important humoral
pattern in HAM/TSP. This response may be used as a diagnostic marker,
considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis
with HAM/TSP and the pathogenesis of this neurological disease. 相似文献
39.
40.
Xiangdan Wang Valerie Quarmby Carl Ng Anan Chuntharapai Theresa Shek Charles Eigenbrot Robert F. Kelley Steven Shia Krista M McCutcheon John Lowe Cecilia Leddy Kyle Coachman Gary Cain Felix Chu Isidro Hotzel Mauricio Maia Eric Wakshull Jihong Yang 《MABS-AUSTIN》2013,5(4):540-554
Pharmacokinetic (PK) and immunohistochemistry (IHC) assays are essential to the evaluation of the safety and efficacy of therapeutic monoclonal antibodies (mAb) during drug development. These methods require reagents with a high degree of specificity because low concentrations of therapeutic antibody need to be detected in samples containing high concentrations of endogenous human immunoglobulins. Current assay reagent generation practices are labor-intensive and time-consuming. Moreover, these practices are molecule-specific and so only support one assay for one program at a time. Here, we describe a strategy to generate a unique assay reagent, 10C4, that preferentially recognizes a panel of recombinant human mAbs over endogenous human immunoglobulins. This “panel-specific” feature enables the reagent to be used in PK and IHC assays for multiple structurally-related therapeutic mAbs. Characterization revealed that the 10C4 epitope is conformational, extensive and mainly composed of non-CDR residues. Most key contact residues were conserved among structurally-related therapeutic mAbs, but the combination of these residues exists at low prevalence in endogenous human immunoglobulins. Interestingly, an indirect contact residue on the heavy chain of the therapeutic appears to play a critical role in determining whether or not it can bind to 10C4, but has no affect on target binding. This may allow us to improve the binding of therapeutic mAbs to 10C4 for assay development in the future. Here, for the first time, we present a strategy to develop a panel-specific reagent that can expedite the development of multiple clinical assays for structurally-related therapeutic mAbs. 相似文献