全文获取类型
收费全文 | 57355篇 |
免费 | 5124篇 |
国内免费 | 1940篇 |
专业分类
耳鼻咽喉 | 650篇 |
儿科学 | 1012篇 |
妇产科学 | 623篇 |
基础医学 | 11353篇 |
口腔科学 | 972篇 |
临床医学 | 3600篇 |
内科学 | 8924篇 |
皮肤病学 | 1255篇 |
神经病学 | 4162篇 |
特种医学 | 934篇 |
外国民族医学 | 16篇 |
外科学 | 4482篇 |
综合类 | 6694篇 |
现状与发展 | 9篇 |
预防医学 | 2286篇 |
眼科学 | 664篇 |
药学 | 9534篇 |
2篇 | |
中国医学 | 2314篇 |
肿瘤学 | 4933篇 |
出版年
2024年 | 152篇 |
2023年 | 1144篇 |
2022年 | 2370篇 |
2021年 | 2432篇 |
2020年 | 1932篇 |
2019年 | 2283篇 |
2018年 | 2380篇 |
2017年 | 2294篇 |
2016年 | 1994篇 |
2015年 | 2332篇 |
2014年 | 3322篇 |
2013年 | 3924篇 |
2012年 | 3386篇 |
2011年 | 4044篇 |
2010年 | 3150篇 |
2009年 | 3133篇 |
2008年 | 2884篇 |
2007年 | 2619篇 |
2006年 | 2321篇 |
2005年 | 1906篇 |
2004年 | 1795篇 |
2003年 | 1492篇 |
2002年 | 1133篇 |
2001年 | 867篇 |
2000年 | 846篇 |
1999年 | 698篇 |
1998年 | 687篇 |
1997年 | 663篇 |
1996年 | 544篇 |
1995年 | 581篇 |
1994年 | 486篇 |
1993年 | 416篇 |
1992年 | 348篇 |
1991年 | 328篇 |
1990年 | 290篇 |
1989年 | 242篇 |
1988年 | 186篇 |
1987年 | 188篇 |
1986年 | 192篇 |
1985年 | 345篇 |
1984年 | 407篇 |
1983年 | 248篇 |
1982年 | 283篇 |
1981年 | 227篇 |
1980年 | 200篇 |
1979年 | 157篇 |
1978年 | 113篇 |
1977年 | 111篇 |
1976年 | 127篇 |
1975年 | 86篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
111.
Stanislw Ryng Zdzislw Machn Zbigniew Wieczorek Michal Zimecki Tadeusz Glowiak 《Archiv der Pharmazie》1997,330(11):319-326
A series of 5-aminomethinimino-3-methyl-4-isoxazolecarboxylic acid phenylamides 4 has been prepared by condensation of 5-amino-3-methyl-4-isoxazolecarboxylic acid phenylamides 1 with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives 2 gave 5-alkoxymethine derivatives 3 which, on reaction with an appropriate amine, formed the corresponding compounds 4 . The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response ( 4d ), humoral immune response ( 4a ), or cellular immune response ( 4c ). Preparation 4d is comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combating pathogen invasion. 相似文献
112.
Nicoletta Desideri Isabella Sestili Maria Luisa Stein Stefano Manarini Giuseppe Dell'Elba Chiara Cerletti 《Archiv der Pharmazie》1997,330(4):100-106
6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B4 and thromboxane B2 production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors. 相似文献
113.
Hiroki Hamanaka Nobuaki Maeda Masaharu Noda 《The European journal of neuroscience》1997,9(11):2297-2308
Protein tyrosine phosphatase ζ (PTPζRPTPβ) is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. In addition to the transmembrane form (PTPζ-A), the extracellular splice variant (PTPζ-S) occurs as a major soluble chondroitin sulphate proteoglycan in the brain. We prepared antibodies which specifically recognize PTPζ-A and -S, and analysed the carbohydrate structures on the two PTPζ isoforms in the developing chick brain. lmmunoprecipitation experiments using these antibodies revealed that almost all of the keratan sulphate recognized by a monoclonal antibody (5D4) was exclusively bound to PTPζ-A and PTPζ-S. Addition of keratan sulphate to these proteoglycans markedly increased from embryonic day (E) 11, in contrast to the addition of LeX and HNK-1 carbohydrates, which gradually increased during development in accordance with expression of the core proteins, suggesting that keratan sulphate modification plays some specific roles. Moreover, at the early embryonic stage keratan sulphate was observed only in several restricted regions, especially at boundary regions such as the roof plate of the tectum, the zona limitans intrathalamica in the diencephalon, and the mesencephalon-metencephalon boundary. At the mesencephalon-metencephalon boundary, keratan sulphate modification of PTPζ isoforms was specifically observed from E3 to E6 on a ring of cells encircling the neural tube and their radially oriented processes, which were identified as radial glial fibres. This expression pattern of keratan sulphate spatiotemporally corresponded well to the formation of the fovea isthmi, a groove separating the mesencephalon from the metencephalon. These results suggest that carbohydrates including keratan sulphate on PTPζ isoforms play important roles in brain development by modulating the cell-cell and/or cell-substrate interactions mediated by these molecules. 相似文献
114.
Macrophages, dendritic cells or B lymphocytes have been shownto play a major role in the presentation of soluble antigensto CD4+ T cells. In contrast, the capacity of these cells topresent particulate antigens such as bacterial or parasiticantigens to T cells remains controversial. To investigate thisquestion, well defined particulate antigens were prepared bycovalent linkage of proteins or peptides to 1 µm in diametersynthetic microspheres. The T cell immunogenicity of such particulateantigens was analyzed in vitro and in vivo. In vitro, a solubleprotein such as hen egg lysozyme (HEL) coupled to beads stimulateda strong proliferative T cell response of lymph node cells fromHEL-primed mice or of specific T cell hybridomas. HEL coupledto beads was presented to the specific T cell hybridomas bysplenocytes or by peritoneal macrophages, but not by lymphomaB cells. Immunization of mice with several different proteinantigens or with a synthetic peptide covalently linked to beadsinduced strong CD4+ T cell responses in the absence of adjuvant.The strong in vivo immunogenicity of proteins coupled to beadsdid not result from a non-specific adjuvant effect of beadssince covalent linkage of the antigen to beads was strictlyrequired to induce T cell responses in the absence of adjuvant.In vivo treatment by carrageenan showed that macrophages arerequired for the in vivo stimulation of T cell responses bythese particulate antigens. Thus, these results demonstratedthe role of phagocytic cells, especially macrophages, for invivo presentation of particulate antigens. These particulateantigens represent an interesting approach for the developmentof new vaccines, and for the in vivo analysis of the role ofvarious antigen presenting cells in T cell activation and differentiation. 相似文献
115.
Manuel Modolell Ines M. Corraliza Franz Link Germn Soler Klaus Eichmann 《European journal of immunology》1995,25(4):1101-1104
Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase. Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline. NO is important in the bactericidal and cytotoxic activities of macrophages. An equivalent functional role of arginase and its products is not known. We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-γ (IFN-γ), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E2 (PGE2). We find that PGE2 and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase. In contrast, the TH 1 cytokine IFN-γ does not induce arginase. Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase. Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase. Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase. The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena. The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH 1 and TH 2 cytokines, respectively. 相似文献
116.
This study demonstrates that ZnSO4 induced chemical trauma results in an in situ regeneration of the olfactory epithelium which, when maintained in vitro, provides an enriched population of olfactory neurons. Therefore, the ability of the olfactory epithelium to respond to chemical trauma with increased mitotic activity can be used to increase growth of neurons in culture. Tissue obtained from normal or vehicle-treated adult mice produced few olfactory neurons, when maintained in culture, compared to cultures established from tissue following an in situ ZnSO4 trauma. Maximal neuronal yields were obtained in cultures established from tissue that was removed 4–6 days following chemical trauma. The morphological appearance and the presence of cell specific intermediate filament proteins were used to classify the cell types in these olfactory epithelial cultures. Single cells and aggregates of cells which were immunopositive for keratin, but immunonegative for neurofilament protein and GFAP, were identified as epithelioid. Flattened polygonal cells immunopositive for GFAP were identified as glia. A small population of flattened cells was immunonegative for all of the antibodies used in this study. Cells that had processes were immunonegative for GFAP and keratin. Some were immunopositive for 200 kDa and 160 kDa neurofilament proteins but immunonegative for the 68 kDa neurofilament protein. A few of these cells showed positive immunoreactivity with the olfactory marker protein (OMP) antibody and most likely represented the most mature olfactory neurons in the cultures. This trauma-induced culture model using olfactory tissue from adult mice can serve as a source of CNS neurons for comparison with cultured embryonic neurons. 相似文献
117.
Nakamura Hajime; De Rosa Stephen; Roederer Mario; Anderson Michael T.; Dubs J. Gregson; Yodoi Junji; Holmgren Arne; Herzenberg Leonard A.; Herzenberg Leonore A. 《International immunology》1996,8(4):603-611
Thioredoxin (Trx), a ubiquitous protein intimately involvedin redox and protein disulfide reductions, has been shown tobe released from cells and to have cytokine-like activities.In addition, Trx has been implicated in the redox regulationof immunological responses and shown to be deficient in tissuesfrom AIDS patients. In studies presented here, plasma Trx levelswere measured by ELISA in plasma samples from HIV-infected individuals(n = 136) and HIV-negative controls (n = 47). To account forthe release of Trx into plasma due to hemolysis, the Trx measurementswere corrected according to the level of hemoglobin in the plasmasample. Data presented show that, in contrast to tissue Trxlevels, corrected plasma Trx levels are significantly higherin HIV-infected individuals than in controls (P < 0.0001).Furthermore, {small tilde}25% of the HIV-infected individualsstudied have plasma Trx levels greater than the highest levelfound in controls (37 ng/ml). Detailed multiparameter FACS analysisof peripheral blood mononuclear cells (PBMC) from the infectedindividuals demonstrates that those with higher plasma Trx levels(37 ng/ml or greater) tend to have lower overall CD4 counts.In addition, increases in plasma Trx levels correlate with decreasesin monochlorobimane staining (indicative of lower intracellularglutathione levels in PBMC) and with changes in surface antigenexpression (CD62L, CD38 and CD20) that occur in the later stagesof HIV infection. These correlations suggest that elevationof plasma Trx levels may be an important component of advancedHIV disease, perhaps related to the oxidative stress that oftenoccurs at this stage. 相似文献
118.
K. Hamano Hiroshi Ito Andrew Bushell Kathryn J. Wood Kensuke Esato 《Transplant international》1997,10(4):293-298
In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation
was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival.
The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose
treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant
effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level
of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence
of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced
by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined
use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were
used concurrently at the time of transplantation.
Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997 相似文献
119.
Klaus Edvardsen Nils Brünner Mogens Spang-Thomsen Frank S. Walsh Elisabeth Bock 《International journal of developmental neuroscience》1993,11(5)
A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those induced by NCAM negative cells. This implies that NCAM may not only be involved in adhesive and motile behaviour of glioma cells, but also in their growth regulation. 相似文献
120.
本文以 E.coli CM891为靶细胞,用细菌内抗突变作用模式研究了肉桂醛,鞣酸,二烯丙三硫的抗4NQO 突变性及其作用机制。含质粒 pKM101的 CM891的高抗株(抗50μg/ml 氨苄青霉素)能提高该菌株的自发突变率和4NQO 诱发的突变率以及对鞣酸的杀伤抗性。肉桂醛的抗突变性不依赖质粒 pKM101效应,但与暂时性生长延搁有关。鞣酸及二烯丙三硫的抗突变机制可能包括质粒 pKM101介导的易误修复。上述三种化学物中每二种联合应用均显示抗4NQO 突变性的协同效应及对靶细胞的毒性杀伤作用。 相似文献