全文获取类型
收费全文 | 1618篇 |
免费 | 121篇 |
国内免费 | 2篇 |
出版年
2023年 | 7篇 |
2022年 | 24篇 |
2021年 | 29篇 |
2020年 | 21篇 |
2019年 | 23篇 |
2018年 | 42篇 |
2017年 | 37篇 |
2016年 | 51篇 |
2015年 | 82篇 |
2014年 | 88篇 |
2013年 | 114篇 |
2012年 | 124篇 |
2011年 | 111篇 |
2010年 | 84篇 |
2009年 | 78篇 |
2008年 | 98篇 |
2007年 | 103篇 |
2006年 | 102篇 |
2005年 | 82篇 |
2004年 | 76篇 |
2003年 | 63篇 |
2002年 | 59篇 |
2001年 | 17篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 20篇 |
1997年 | 14篇 |
1996年 | 11篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 13篇 |
1991年 | 18篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 11篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1972年 | 4篇 |
1968年 | 2篇 |
排序方式: 共有1741条查询结果,搜索用时 18 毫秒
931.
Maturation of blood-derived dendritic cells enhances human immunodeficiency virus type 1 capture and transmission 总被引:3,自引:2,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Izquierdo-Useros N Blanco J Erkizia I Fernández-Figueras MT Borràs FE Naranjo-Gómez M Bofill M Ruiz L Clotet B Martinez-Picado J 《Journal of virology》2007,81(14):7559-7570
Dendritic cells (DCs) are specialized antigen-presenting cells. However, DCs exposed to human immunodeficiency virus type 1 (HIV-1) are also able to transmit a vigorous cytopathic infection to CD4(+) T cells, a process that has been frequently related to the ability of DC-SIGN to bind HIV-1 envelope glycoproteins. The maturation of DCs can increase the efficiency of HIV-1 transmission through trans infection. We aimed to comparatively study the effect of maturation in monocyte-derived DCs (MDDCs) and blood-derived myeloid DCs during the HIV-1 capture process. In vitro capture and transmission of envelope-pseudotyped HIV-1 and its homologous replication-competent virus to susceptible target cells were assessed by p24(gag) detection, luciferase activity, and both confocal and electron microscopy. Maturation of MDDCs or myeloid DCs enhanced the active capture of HIV-1 in a DC-SIGN- and viral envelope glycoprotein-independent manner, increasing the life span of trapped virus. Moreover, higher viral transmission of mature DCs to CD4(+) T cells was highly dependent on active viral capture, a process mediated through cholesterol-enriched domains. Mature DCs concentrated captured virus in a single large vesicle staining for CD81 and CD63 tetraspanins, while immature DCs lacked these structures, suggesting different intracellular trafficking processes. These observations help to explain the greater ability of mature DCs to transfer HIV-1 to T lymphocytes, a process that can potentially contribute to the viral dissemination at lymph nodes in vivo, where viral replication takes place and there is a continuous interaction between susceptible T cells and mature DCs. 相似文献
932.
The pep4 gene encoding proteinase A is involved in dimorphism and pathogenesis of Ustilago maydis
下载免费PDF全文
![点击此处可从《Molecular Plant Pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cinthia V. Soberanes‐Gutiérrez Margarita Juárez‐Montiel Omar Olguín‐Rodríguez César Hernández‐Rodríguez José Ruiz‐Herrera Lourdes Villa‐Tanaca 《Molecular Plant Pathology》2015,16(8):837-846
Vacuole proteases have important functions in different physiological processes in fungi. Taking this aspect into consideration, and as a continuation of our studies on the analysis of the proteolytic system of Ustilago maydis, a phytopathogenic member of the Basidiomycota, we have analysed the role of the pep4 gene encoding the vacuolar acid proteinase PrA in the pathogenesis and morphogenesis of the fungus. After confirmation of the location of the protease in the vacuole using fluorescent probes, we obtained deletion mutants of the gene in sexually compatible strains of U. maydis (FB1 and FB2), and analysed their phenotypes. It was observed that the yeast to mycelium dimorphic transition induced by a pH change in the medium, or the use of a fatty acid as sole carbon source, was severely reduced in Δpep4 mutants. In addition, the virulence of the mutants in maize seedlings was reduced, as revealed by the lower proportion of plants infected and the reduction in size of the tumours induced by the pathogen, when compared with wild‐type strains. All of these phenotypic alterations were reversed by complementation of the mutant strains with the wild‐type gene. These results provide evidence of the importance of the pep4 gene for the morphogenesis and virulence of U. maydis. 相似文献
933.
934.
María de Lourdes Ramírez‐Ahuja Mayra A. Gmez‐Govea Angel Lugo‐Trampe Gissela Borrego‐Soto Ivn Delgado‐Enciso Gustavo Ponce‐Garcia Margarita L. Martínez‐Fierro Eda G. Ramírez‐Valles Víctor Trevio Adriana E. Flores‐Suarez Iram P. Rodríguez‐Sanchez 《Journal of Applied Entomology》2019,143(8):834-841
The microbiota of Hymenoptera is limited to certain bacterial species that vary according to the habitat and diet; however, the bacterial populations are not known in Telenomus tridentatus Johnson & Bin, an egg parasitoid of agricultural importance. We determined the microbiota composition of adults of T. tridentatus using next‐generation sequencing technologies. We found the presence of the Phylums Proteobacteria, in greater proportion followed by Actinobacteria and Firmicutes, respectively. The most abundant species were Cutibacterium acnes, Aquabacterium sp. and Massilia sp. The results of this study could lead to investigating the importance of symbiotic bacteria in T. tridentatus and its relation with agricultural plantations. 相似文献
935.
936.
Murillo MM Carmona-Cuenca I Del Castillo G Ortiz C Roncero C Sánchez A Fernández M Fabregat I 《The Biochemical journal》2007,405(2):251-259
The TGF-beta (transforming growth factor-beta) induces survival signals in foetal rat hepatocytes through transactivation of EGFR (epidermal growth factor receptor). The molecular mechanism is not completely understood, but both activation of the TACE (tumour necrosis factor alpha-converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17; one of the metalloproteases involved in shedding of the EGFR ligands) and up-regulation of TGF-alpha and HB-EGF (heparin-binding epidermal growth factor-like growth factor) appear to be involved. In the present study, we have analysed the molecular mechanisms that mediate up-regulation of the EGFR ligands by TGF-beta in foetal rat hepatocytes. The potential involvement of ROS (reactive oxygen species), an early signal induced by TGF-beta, and the existence of an amplification loop triggered by initial activation of the EGFR, have been studied. Results indicate that DPI (diphenyleneiodonium) and apocynin, two NOX (NADPH oxidase) inhibitors, and SB431542, an inhibitor of the TbetaR-I (TGF-beta receptor I), block up-regulation of EGFR ligands and Akt activation. Different members of the NOX family of genes are expressed in hepatocytes, included nox1, nox2 and nox4. TGF-beta up-regulates nox4 and increases the levels of Rac1 protein, a known regulator of both Nox1 and Nox2, in a TbetaR-I-dependent manner. TGF-beta mediates activation of the nuclear factor-kappaB pathway, which is inhibited by DPI and is required for up-regulation of TGF-alpha and HB-EGF. In contrast, EGFR activation is not required for TGF-beta-induced up-regulation of those ligands. Considering previous work that has established the role of ROS in apoptosis induced by TGF-beta in hepatocytes, the results of the present study indicate that ROS might mediate both pro- and anti-apoptotic signals in TGF-beta-treated cells. 相似文献
937.
Structures of phi29 DNA polymerase complexed with substrate: the mechanism of translocation in B-family polymerases 总被引:2,自引:0,他引:2
Berman AJ Kamtekar S Goodman JL Lázaro JM de Vega M Blanco L Salas M Steitz TA 《The EMBO journal》2007,26(14):3494-3505
Replicative DNA polymerases (DNAPs) move along template DNA in a processive manner. The structural basis of the mechanism of translocation has been better studied in the A-family of polymerases than in the B-family of replicative polymerases. To address this issue, we have determined the X-ray crystal structures of phi29 DNAP, a member of the protein-primed subgroup of the B-family of polymerases, complexed with primer-template DNA in the presence or absence of the incoming nucleoside triphosphate, the pre- and post-translocated states, respectively. Comparison of these structures reveals a mechanism of translocation that appears to be facilitated by the coordinated movement of two conserved tyrosine residues into the insertion site. This differs from the mechanism employed by the A-family polymerases, in which a conserved tyrosine moves into the templating and insertion sites during the translocation step. Polymerases from the two families also interact with downstream single-stranded template DNA in very different ways. 相似文献
938.
Gutiérrez S Mukdsi JH Aoki A Torres AI Soler AP Orgnero EM 《Cell and tissue research》2007,327(1):121-132
We have investigated the expression of receptors for insulin and insulin-like growth factor 1 (IGF-1) in rat pituitary cells in vitro and examined the morphological and proliferative changes induced in adenohypophyseal cells by insulin and IGF-1. The proliferation of lactotrophs was determined by double-immunostaining for bromodeoxyuridine and prolactin. Incubation with insulin (10, 100 or 1000 ng/ml) or IGF-1 (5, 30 or 100 ng/ml) for 48 or 72 h significantly increased the number of lactotrophs undergoing mitosis. Co-incubation of insulin or IGF-1 with genistein (25 μM), an inhibitor of the tyrosine kinase receptor, reduced the proliferation of lactotrophs elicited by the hormone and the growth factor. The receptors for insulin and IGF-1 were localized in intact pituitary cells by ultrastructural immunocytochemistry with the colloidal gold-protein A technique. Gonadotrophs expressed both receptors, specific labelling being restricted to this cell type. Electron-microscopical observations of pituitary cell cultures incubated with insulin or IGF-1 revealed gonadotroph cells exhibiting the fine-structural features of enhanced protein synthetic activity. These findings suggest that both insulin and IGF-1 are able to induce the proliferation of lactotrophs through an indirect mechanism mediated by a factor synthesized by gonadotroph cells, in addition to stimulating the biosynthetic activity of the gonadotroph in a direct manner.This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT). 相似文献
939.
Serrano-Heras G Ruiz-Masó JA del Solar G Espinosa M Bravo A Salas M 《Nucleic acids research》2007,35(16):5393-5401
Protein p56 (56 amino acids) from the Bacillus subtilis phage ϕ29 inactivates the host uracil-DNA glycosylase (UDG), an enzyme involved in the base excision repair pathway. At present, p56 is the only known example of a UDG inhibitor encoded by a non-uracil containing viral DNA. Using analytical ultracentrifugation methods, we found that protein p56 formed dimers at physiological concentrations. In addition, circular dichroism spectroscopic analyses revealed that protein p56 had a high content of β-strands (around 40%). To understand the mechanism underlying UDG inhibition by p56, we carried out in vitro experiments using the Escherichia coli UDG enzyme. The highly acidic protein p56 was able to compete with DNA for binding to UDG. Moreover, the interaction between p56 and UDG blocked DNA binding by UDG. We also demonstrated that Ugi, a protein that interacts with the DNA-binding domain of UDG, was able to replace protein p56 previously bound to the UDG enzyme. These results suggest that protein p56 could be a novel naturally occurring DNA mimicry. 相似文献
940.
Romero-Avila M de Dios-Bravo G Mendez-Stivalet JM Rodríguez-Sotres R Iglesias-Arteaga MA 《Steroids》2007,72(14):955-959
Two furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety were synthesized and their biological activity studied using the bean second internode elongation test. One of the compounds produced significant stimulation at doses of 2.5 and 5ng/plant. 相似文献