全文获取类型
收费全文 | 10248篇 |
免费 | 556篇 |
国内免费 | 78篇 |
专业分类
耳鼻咽喉 | 116篇 |
儿科学 | 228篇 |
妇产科学 | 186篇 |
基础医学 | 1332篇 |
口腔科学 | 240篇 |
临床医学 | 1045篇 |
内科学 | 2478篇 |
皮肤病学 | 142篇 |
神经病学 | 1167篇 |
特种医学 | 352篇 |
外科学 | 1663篇 |
综合类 | 13篇 |
预防医学 | 297篇 |
眼科学 | 105篇 |
药学 | 614篇 |
中国医学 | 12篇 |
肿瘤学 | 892篇 |
出版年
2024年 | 10篇 |
2023年 | 55篇 |
2022年 | 152篇 |
2021年 | 218篇 |
2020年 | 133篇 |
2019年 | 180篇 |
2018年 | 253篇 |
2017年 | 210篇 |
2016年 | 251篇 |
2015年 | 239篇 |
2014年 | 366篇 |
2013年 | 500篇 |
2012年 | 782篇 |
2011年 | 717篇 |
2010年 | 401篇 |
2009年 | 390篇 |
2008年 | 674篇 |
2007年 | 643篇 |
2006年 | 684篇 |
2005年 | 668篇 |
2004年 | 690篇 |
2003年 | 602篇 |
2002年 | 512篇 |
2001年 | 113篇 |
2000年 | 88篇 |
1999年 | 92篇 |
1998年 | 117篇 |
1997年 | 87篇 |
1996年 | 95篇 |
1995年 | 84篇 |
1994年 | 73篇 |
1993年 | 76篇 |
1992年 | 78篇 |
1991年 | 71篇 |
1990年 | 49篇 |
1989年 | 56篇 |
1988年 | 44篇 |
1987年 | 39篇 |
1986年 | 47篇 |
1985年 | 39篇 |
1984年 | 42篇 |
1983年 | 31篇 |
1982年 | 38篇 |
1981年 | 33篇 |
1980年 | 29篇 |
1979年 | 16篇 |
1978年 | 17篇 |
1977年 | 13篇 |
1975年 | 10篇 |
1972年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
41.
Ligand and cytokine dependence of the immunosuppressive pathway of tryptophan catabolism in plasmacytoid dendritic cells 总被引:3,自引:0,他引:3
Fallarino F Orabona C Vacca C Bianchi R Gizzi S Asselin-Paturel C Fioretti MC Trinchieri G Grohmann U Puccetti P 《International immunology》2005,17(11):1429-1438
Murine plasmacytoid dendritic cells (pDCs) have been credited with a unique ability to express indoleamine 2,3-dioxygenase (IDO) function and mediate immunosuppression in specific settings; yet, the conditions of spontaneous versus induced activity have remained unclear. We have used maneuvers known to up-regulate IDO in different cell types and have examined the relative efficacy and mechanisms of the induced activity in splenic pDCs, namely, after specific receptor engagement by CTLA-4-Ig, CD200-Ig or CD28-Ig, the latter in combination with silenced expression of the suppressor of cytokine signaling 3 (SOCS3) gene. We found that pDCs (CD11c+ mPDCA-1+ 120G8+) do not express IDO and are not tolerogenic under basal conditions. B7-1 engagement by CTLA-4-Ig, CD200R1 engagement by CD200-Ig and B7-1/B7-2 engagement by CD28-Ig in SOCS3-deficient pDCs were each capable of initiating IDO-dependent tolerance via different mechanisms. IFN-gamma was the major cytokine responsible for CTLA-4-Ig effects, and type I IFNs for those of CD200-Ig. Immunosuppression by CD28-Ig in the absence of SOCS3 required IFN-gamma induction and IFN-like actions of IL-6. Therefore, although pDCs do not mediate IDO-dependent tolerance constitutively, multiple ligands and cytokines will contribute to the expression of a tolerogenic phenotype by pDCs in the mouse. 相似文献
42.
Josep Sul-Suso Flavio Arienti Cecilia Melani Mario Paolo Colombo Giorgio Parmiani 《European journal of immunology》1995,25(10):2737-2742
B7 co-stimulation is necessary to activate resting T cells upon antigen recognition by the T cell receptor. To see whether expression of B7 may render human melanoma cells able to stimulate T cells, a cloned melanoma line (Me1B6), which did not express B7-1, was transfected with the human B7-1 gene. In proliferation assays, B7-1 transfected cells (Me1B6/B7) showed greater stimulatory activity of allogeneic and autologous peripheral blood lymphocytes (PBL) compared to parental, non-transfected tumor cells. This effect was also seen when allogeneic CD8+ and CD4+ subpopulations were used as effectors. In these studies, activation of lymphocytes was B7-1-dependent and HLA classes I and II mediated. The higher proliferation correlated with an increased lytic activity by PBL stimulated with B7-1+ tumor cells against the untransfected Me1B6. Furthermore, PBL from a metastatic melanoma patient stimulated by Me1B6/B7 developed an higher lytic activity not only against Me1B6 but also against their autologous, B7-1? tumor. Finally, after Me1B6/B7 stimulation, PBL released interleukin (IL)-2 and interferon-γ, but not IL-4, suggesting a Th1-mediated response. These data support the use of B7-1 transfected melanoma cells in the therapeutic vaccination of melanoma patients. 相似文献
43.
Giuliana Properzi Sandro Franca Villa Gianfranco Poccia Paolo Aloisi Xu-Hong Gu Giorgio Terenghi Julia M. Polak 《The Journal of pathology》1993,169(2):269-277
Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18–46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n=6), with diabetes for 6 months to 3 years; group 2 (n=5), with the disease for 5–10 years; and group 3 (n=7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P <0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P <0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (>95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (<5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P=0·002), presence of clinical autonomic neuropathy (Fisher exact test P=0.04), and a reduced sural nerve conduction velocity (Fisher exact test P=0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests. 相似文献
44.
Giorgio Torelli Eloisa Milla Leonard I. Kleinman Alide Faelli 《Pflügers Archiv : European journal of physiology》1973,342(3):219-230
Summary The relationship between sodium reabsorption and oxygen consumption was studied in an isolated rabbit kidney preparation perfused with blood at 37, 28 and 19° C. When the temperature was lowered from 37° C to 28° C and to 19°C the rate of oxygen consumption and of the maximal P.A.H. excretion (Tm P.A.H.) decreased more than that of sodium reabsorption.TheQ
10 for sodium reabsorption is about 1.8, while that for maximal P.A.H. excretion is 2.5. Some hypothesis on the possible mechanisms of the lowQ
10 of the Na+ reabsorption are forwarded.Preliminary reports have been published [Boll. Soc. Ital. Biol. Sper.43, 1019–1023 (1966) and44, 1784–1787 (1967);45, 860–862 (1969) and45, 863–865 (1969)]. 相似文献
45.
Annunziata I Lanzara C Conte I Zullo A Ventruto V Rinaldi MM D'Urso M Casari G Ciccodicola A Miano MG 《American journal of medical genetics. Part A》2003,(3):217-222
X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene. 相似文献
46.
Paola Borgatti Giorgio Zauli Maria Luisa Colamussi Davide Gibellini Maurizio Previati Lewis L. Cantley Silvano Capitani 《European journal of immunology》1997,27(11):2805-2811
The biological basis for the pleiotropic activity of extracellular human immunodeficiency virus (HIV)-1 Tat protein on lymphoid T cell survival is not well understood. We have here demonstrated that the addition in culture of 0.1–10 nM Tat protein to 36-h serum-starved lymphoblastoid Jurkat T cells rapidly stimulates the catalytic activity of phosphatidylinositol 3-kinase (PI 3-K). The peak of activation was observed 30 min after Tat addition. Extracellular Tat also stimulated the catalytic activity of the Akt/PKB kinase, a major target of PI 3-K lipid products. Pretreatment of serum-starved Jurkat cells with 100 nM wortmannin (WT) or 10 μM LY294002, two unrelated pharmacological inhibitors of PI 3-K, markedly suppressed the catalytic activity of both PI 3-K and Akt/PKB in Jurkat cells. Moreover, at low concentrations (0.1–1 nM), extracellular Tat showed a small but reproducible protection of Jurkat cells from apoptosis induced by serum deprivation (p < 0.05), while the combination of Tat plus 100 nM WT significantly (p < 0.05) increased the percentage of apoptosis with respect to cells left untreated or treated with Tat alone. Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway. 相似文献
47.
It was proposed recently that CEM CD4-positive T cells infected chronically by herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus type 1 (HIV-1) (CEM(HSV/HIV)) may be used as a model for studying HIV/HSV interactions. To ascertain whether HSV-HIV coinfection of T lymphocytes has a role in promoting progression of lentiviral infection, T cells infected chronically by either HSV-1 (CEM(HSV)) or HIV-1 (CEM(HIV)) were challenged with a superinfecting dose of HIV-1 or HSV-1. The results show a positive influence on HIV growth when CEM(HIV) cells were superinfected with HSV-1 to an extent that was dependent on the multiplicity of superinfection used. In contrast, HIV superinfection of CEM(HSV) cells resulted in a delay of HIV-1 production and in a lack of HSV-mediated LTR transactivation. These effects were due to cell growth inhibition and apoptosis, resulting from persistent HSV-1 infection. Treatment of CEM(HSV) with acyclovir inhibited completely the HSV-1 cytopathic effects and allowed efficient HIV-1 replication. These data may be relevant in clarifying the role of HIV/HSV interaction in the pathogenesis of AIDS. 相似文献
48.
Patrizia Nanni Carla De Giovanni Pier-Luigi Lollini Giordano Nicoletti Giorgio Prodi 《Clinical & experimental metastasis》1983,1(4):373-380
A metastasizing mouse cell line (TS/A), originated from a mammary adenocarcinoma which arose spontaneously in a BALB/c female retired breeder, has been established in vitro. It displayed a remarkable morphologic heterogeneity, which is evident in plastic adherent cultures (cell types ranging from epithelial-like to fibroblast-like) as well as in semi-solid agar cultures. The TS/A line exhibited the presence of specific cytoplasmic estradiol receptor, with a binding activity of 16 fmoles/mg cytosol protein. The in vivo growth pattern was as follows: (1) a s.c. inoculum of 105 cells caused a 100 per cent tumor take and kill in syngeneic animals; mean survival time was 54 + 1 days; (2) it did not show significant transplant immunogenicity in syngeneic animals; (3) it was able to give rise to both spontaneous lung metastases and artificial lung colonies; (4) it had a high capacity to grow in H-2 matched, minor histocompatibility antigen incompatible hosts (106 cells killed 100 per cent DBA/2 mice in 58 + 2 days). This line of spontaneous mammary tumor cells is proposed as a useful model for studies on the heterogeneity of the neoplastic population in relation to metastatic spread, on tumor immunogenicity, and on therapy of mammary neoplasia. 相似文献
49.
Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients 下载免费PDF全文
50.
Immunofluorescent detection of anti-cytoskeleton antibodies using vinblastine-treated mononuclear cells 总被引:2,自引:0,他引:2
A reliable and reproducible immunofluorescence method is described for the detection of anti-cytoskeleton antibodies in human sera, based on the use of vinblastine-treated peripheral blood mononuclear cells as substrate. Three immunofluorescence patterns associated with antibodies to microfilaments, intermediate filaments and microtubules are readily identified. 相似文献