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991.
Christiane Mariotini-Moura Matheus Silva e Bastos Felipe Freitas de Castro Mellina Lanna Trindade Raphael de Souza Vasconcellos Myrian Augusta Araújo Neves-do-Valle Bernardo Pereira Moreira Ramon de Freitas Santos Claudia Miranda de Oliveira Luana Celina Seraphim Cunha Xênia Macedo Souto Gustavo Costa Bressan Abelardo Silva-Júnior Munira Muhammad Abdel Baqui Maria Terezinha Bahia Márcia Rogéria de Almeida José Roberto Meyer-Fernandes Juliana Lopes Rangel Fietto 《Acta tropica》2014
Previous work has suggested that Trypanosoma cruzi diphosphohydrolase 1 (TcNTPDase-1) may be involved in the infection of mammalian cells and serve as a potential target for rational drug design. In this work, we produced recombinant TcNTPDase-1 and evaluated its nucleotidase activity, cellular localization and role in parasite adhesion to mammalian host cells. TcNTPDase-1 was able to utilize a broad range of triphosphate and diphosphate nucleosides. The enzyme's Km for ATP (0.096 mM) suggested a capability to influence the host's ATP-dependent purinergic signaling. The use of specific polyclonal antibodies allowed us to confirm the presence of TcNTPDase-1 at the surface of parasites by confocal and electron microscopy. In addition, electron microscopy revealed that TcNTPDase-1 was also found in the flagellum, flagellum insertion region, kinetoplast, nucleus and intracellular vesicles. The presence of this enzyme in the flagellum insertion region and vesicles suggests that it may have a role in nutrient acquisition, and the widespread distribution of TcNTPDase-1 within the parasite suggests that it may be involved in other biological process. Adhesion assays using anti-TcNTPDase-1 polyclonal antibodies as a blocker or purified recombinant TcNTPDase-1 as a competitor revealed that the enzyme has a role in parasite–host cell adhesion. These data open new frontiers to future studies on this specific parasite–host interaction and other unknown functions of TcNTPDase-1 related to its ubiquitous localization. 相似文献
992.
993.
William B. Messer Ruklanthi de Alwis Boyd L. Yount Scott R. Royal Jeremy P. Huynh Scott A. Smith James E. Crowe Jr. Benjamin J. Doranz Kristen M. Kahle Jennifer M. Pfaff Laura J. White Carlos A. Sariol Aravinda M. de Silva Ralph S. Baric 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(5):1939-1944
The four dengue virus (DENV) serotypes, DENV-1, -2, -3, and -4, are endemic throughout tropical and subtropical regions of the world, with an estimated 390 million acute infections annually. Infection confers long-term protective immunity against the infecting serotype, but secondary infection with a different serotype carries a greater risk of potentially fatal severe dengue disease, including dengue hemorrhagic fever and dengue shock syndrome. The single most effective measure to control this threat to global health is a tetravalent DENV vaccine. To date, attempts to develop a protective vaccine have progressed slowly, partly because the targets of type-specific human neutralizing antibodies (NAbs), which are critical for long-term protection, remain poorly defined, impeding our understanding of natural immunity and hindering effective vaccine development. Here, we show that the envelope glycoprotein domain I/II hinge of DENV-3 and DENV-4 is the primary target of the long-term type-specific NAb response in humans. Transplantation of a DENV-4 hinge into a recombinant DENV-3 virus showed that the hinge determines the serotype-specific neutralizing potency of primary human and nonhuman primate DENV immune sera and that the hinge region both induces NAbs and is targeted by protective NAbs in rhesus macaques. These results suggest that the success of live dengue vaccines may depend on their ability to stimulate NAbs that target the envelope glycoprotein domain I/II hinge region. More broadly, this study shows that complex conformational antibody epitopes can be transplanted between live viruses, opening up similar possibilities for improving the breadth and specificity of vaccines for influenza, HIV, hepatitis C virus, and other clinically important viral pathogens.The four dengue virus serotypes (DENV-1, -2, -3, and -4), transmitted by Aedes spp. mosquitoes, are endemic throughout tropical and subtropical regions of the world, with an estimated 390 million new infections annually (1). Primary infection with one serotype confers long-term immunity against that serotype, but repeat infection with a different serotype has an increased risk of potentially fatal severe dengue disease (2), including dengue hemorrhagic fever and dengue shock syndrome. This risk has been attributed, at least in part, to the ability of some cross-reactive antibodies to enhance infection of Fc-receptor bearing cells. The consensus is that, to be safe and effective, any dengue vaccine must simultaneously induce neutralizing antibodies (NAbs) to all four serotypes. However, DENV vaccine development has progressed slowly, highlighted by the disappointing results of the live-attenuated Sanofi Pasteur tetravalent DENV vaccine trial in Thailand (3). Progress is hindered, in part, because the epitopes targeted by the type-specific human NAbs critical for long-term protection (4, 5) remain poorly defined, limiting our understanding of natural DENV immunity and slowing effective vaccine development.The DENV envelope glycoprotein (E) (Fig. 1A) is the major surface-exposed DENV antigen and the principle target of NAbs. The E structure consists of three distinct domains: I, II, and III (EDI, EDII, and EDIII) (6, 7); EDIII is a continuous peptide extending from domain I and forming an Ig-like fold, whereas EDI and EDII are discontinuous and connect by four peptide linkers that form the EDI/EDII hinge. We and others have recently described potent human DENV NAbs that bind to epitopes around the EDI/EDII hinge (8, 9). To more fully explore the significance of this antigenic region, we used reverse genetics and synthetic biology to transplant the EDI/EDII antigenic region from DENV-4 into a DENV-3 background and showed by both gain- and loss-of-function assays that the EDI/EDII hinge region is the primary target of the long-lived DENV serotype-specific NAb response.Open in a separate windowFig. 1.(A) Cartoon representation of the DENV-3 E dimer with EDI (red), EDII (yellow), and EDIII (blue). The EDI/EDII hinge region is circled. Location of the critical residues associated with escape mutations and mutagenesis-mapped 5J7 residues are shown. Residues critical for 5J7 binding identified by shotgun mutagenesis loss of binding of E glycoprotein expressed in HEK-293T cells are shown in magenta. Mutations associated with both viral escape from 5J7 and loss of binding in HEK-293T cells (L53 and K128) are shown in orange, and the single residue identified by escape mutation alone (Q269K270_insK) is shown in cyan. All critical residues were individually identified but are shown on a single E dimer for simplicity. (B) Cartoon representation of the DENV E dimer with the locations of variable EDI/EDII hinge residues transplanted between rDENV-3 and rDENV-4 to make rDENV-3/4 shown in green. (C) Primary sequence alignment and secondary structure of rDENV-3 E, rDENV-3/4 E, and rDENV-4 E. Secondary structure is indicated above the primary sequence and color-coded to the corresponding domains on the tertiary structure (A and B). Arrows indicate β-sheets, cylinders indicate helices, and lines indicate spanning loops and strands. Binding, escape, and hinge residues shown in A and B are indicated by corresponding colors in the rDENV-3 sequence. Amino acid residues transplanted between rDENV-3/4 and rDENV-4 are indicated in green for both sequences. 相似文献
994.
995.
996.
Vera Lúcia Corti?o Corrêa Rodrigues Clovis Pauliquevis Junior Rubens Antonio da Silva Dalva Marli Valério Wanderley Marluci Monteiro Guirardo Lilian Aparecida Colebrusco Rodas Claudio Casanova Marcio L. Pachioni Wilson A. Souza Abílio Jose Batista Costa Delvo Baitelo Vera Lúcia Braga Tonietti 《Revista do Instituto de Medicina Tropical de S?o Paulo》2014,56(3):213-218
The objective of this study is to report on the colonization of palm trees
by Rhodnius neglectus, its invasion in an urban area, in Araçatuba -
São Paulo, and the control and surveillance measures that have been put in place.
Domiciliary triatomine searches occurred in apartments upon the inhabitants''
notification. The collected insects were identified and examined for natural
infection and food sources with a precipitin test. To search the palm trees, tarps
were used to cover the floor, and a “Munck” truck equipped with a tree-pruning device
was utilized. Chemical control was performed with the utilization of a manual
compression. In 2009, 81 specimens of Rhodnius neglectus were
collected from the domiciles by the population. The precipitin test revealed a
presence of human blood in 2.7% of the samples. Entomological studies were carried
out in these domiciles and in those located within a radius of 200 meters. The search
performed in the palm trees resulted in the capture of 882 specimens of triatomines,
negative for tripanosomatids. Mechanical and chemical controls were carried out. New
searches conducted in the palm trees in the same year resulted in the capture of six
specimens. The mechanical and chemical controls of the palm trees, together with the
population''s work, proved to be effective, therefore preventing these insects''
colonization of the city''s domiciles. 相似文献
997.
Li? Bárbara Arruda Marilia Ladeira de Araújo Maira Luccia Martinez Claudio Roberto Gonsalez Alberto José da Silva Duarte Eoin Coakley Yolanda Lie Jorge Casseb 《Revista do Instituto de Medicina Tropical de S?o Paulo》2014,56(4):287-290
The clinical application of CCR5 antagonists involves first determining
the coreceptor usage by the infecting viral strain. Bioinformatics programs that
predict coreceptor usage could provide an alternative method to screen candidates for
treatment with CCR5 antagonists, particularly in countries with limited financial
resources. Thus, the present study aims to identify the best approach using
bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice.
Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under
clinical monitoring were analyzed in this study. Based on the Trofile results, the
viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of
tropism using a Geno2pheno[coreceptor] analysis with a false positive rate
of 10% gave the most suitable performance in this sampling: the R5 and X4 strains
were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6%
concordance between the phenotypic and genotypic results. Further studies are needed
to clarify how genetic diversity amongst virus strains affects bioinformatics-driven
approaches for determining tropism. Although this strategy could be useful for
screening patients in developing countries, some limitations remain that restrict the
wider application of coreceptor usage tests in clinical practice. 相似文献
998.
Madelon Novato Ribeiro Maria Inês Fernandes Pimentel Armando de Oliveira Schubach Raquel de Vasconcellos Carvalh?es de Oliveira José Liporage Teixeira Madson Pedro da Silva Leite Monique Fonseca Ginelza Peres Lima dos Santos Mariza Matos Salgueiro Erica de Camargo Ferreira e Vasconcellos Marcelo Rosandiski Lyra Mauricio Naoto Saheki Claudia Maria Valete-Rosalino 《Revista do Instituto de Medicina Tropical de S?o Paulo》2014,56(4):291-296
The favorable outcome of the treatment of a disease is influenced by the
adherence to therapy. Our objective was to assess factors associated with adherence
to treatment of patients included in a clinical trial of equivalence between the
standard and alternative treatment schemes with meglumine antimoniate (MA) in the
treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between
2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect
socioeconomic data. The following methods were used for adherence monitoring:
counting of vial surplus, monitoring card, Morisky test and modified Morisky test
(without the question regarding the schedule); we observed 82.1% (vial return), 86.0%
(monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence.
There was a strong correlation between the method of vial counting and the monitoring
card and modified Morisky test. A significant association was observed between
greater adherence to treatment and low dose of MA, as well as with a lower number of
people sleeping in the same room. We recommend the use of the modified Morisky test
to assess adherence to treatment of CL with MA, because it is a simple method and
with a good performance, when compared to other methods. 相似文献
999.
Resistance Exercise Restores Endothelial Function and Reduces Blood
Pressure in Type 1 Diabetic Rats
Marcelo Mendon?a Mota Tharciano Luiz Teixeira Braga da Silva Milene Tavares Fontes André Sales Barreto Jo?o Eliakim dos Santos Araújo Ant?nio Cesar Cabral de Oliveira Rogério Brand?o Wichi Márcio Roberto Viana Santos 《Arquivos brasileiros de cardiologia》2014,103(1):25-32