全文获取类型
收费全文 | 18974篇 |
免费 | 982篇 |
国内免费 | 416篇 |
专业分类
耳鼻咽喉 | 48篇 |
儿科学 | 204篇 |
妇产科学 | 316篇 |
基础医学 | 2714篇 |
口腔科学 | 305篇 |
临床医学 | 1221篇 |
内科学 | 2854篇 |
皮肤病学 | 333篇 |
神经病学 | 1022篇 |
特种医学 | 291篇 |
外国民族医学 | 6篇 |
外科学 | 1006篇 |
综合类 | 2625篇 |
现状与发展 | 1篇 |
预防医学 | 838篇 |
眼科学 | 248篇 |
药学 | 3881篇 |
6篇 | |
中国医学 | 1492篇 |
肿瘤学 | 961篇 |
出版年
2023年 | 222篇 |
2022年 | 341篇 |
2021年 | 602篇 |
2020年 | 688篇 |
2019年 | 582篇 |
2018年 | 515篇 |
2017年 | 740篇 |
2016年 | 720篇 |
2015年 | 669篇 |
2014年 | 1616篇 |
2013年 | 2379篇 |
2012年 | 1905篇 |
2011年 | 1769篇 |
2010年 | 1314篇 |
2009年 | 1131篇 |
2008年 | 983篇 |
2007年 | 567篇 |
2006年 | 529篇 |
2005年 | 494篇 |
2004年 | 410篇 |
2003年 | 336篇 |
2002年 | 252篇 |
2001年 | 138篇 |
2000年 | 142篇 |
1999年 | 97篇 |
1998年 | 111篇 |
1997年 | 91篇 |
1996年 | 91篇 |
1995年 | 82篇 |
1994年 | 49篇 |
1993年 | 38篇 |
1992年 | 31篇 |
1991年 | 18篇 |
1990年 | 23篇 |
1989年 | 14篇 |
1988年 | 21篇 |
1987年 | 15篇 |
1985年 | 65篇 |
1984年 | 77篇 |
1983年 | 87篇 |
1982年 | 85篇 |
1981年 | 55篇 |
1980年 | 58篇 |
1979年 | 42篇 |
1978年 | 36篇 |
1977年 | 28篇 |
1976年 | 23篇 |
1975年 | 24篇 |
1974年 | 20篇 |
1973年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia
Ying Wang J Peruzzi F Lassak A Del Valle L Radhakrishnan S Rappaport J Khalili K Amini S Reiss K 《Virology》2003,305(1):66-76
Human immunodeficiency virus type 1 (HIV-1) infection often results in disorders of the central nervous system, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-alpha (TNFalpha) released by activated and/or infected macrophages/microglia plays a role in the process of neuronal damage seen in AIDS patients. In light of earlier studies showing that the activation of the insulin-like growth factor I receptor (IGF-IR) exerts a strong neuroprotective effect, we investigated the ability of IGF-I to protect neuronal cells from HIV-infected macrophages. Our results demonstrate that the conditioned medium from HIV-1-infected macrophages, HIV/CM, causes loss of neuronal processes in differentiated PC12 and P19 neurons and that these neurodegenerative effects are associated with the presence of TNFalpha. Furthermore, we demonstrate that IGF-I rescues differentiated neurons from both HIV/CM and TNFalpha-induced damage and that IGF-I-mediated neuroprotection is strongly enhanced by overexpression of the wt IGF-IR cDNA and attenuated by the antisense IGF-IR cDNA. Finally, IGF-I-mediated antiapoptotic pathways are continuously functional in differentiated neurons exposed to HIV/CM and are likely supported by TNFalpha-mediated phosphorylation of I(kappa)B. All together these results suggest that the balance between TNFalpha and IGF-IR signaling pathways may control the extent of neuronal injury in this HIV-related experimental setting. 相似文献
52.
Macrophages play a major role in HIV-1 persistence. In the present paper, we demonstrate that the absence of apoptosis in HIV-1-infected primary human monocyte-differentiated macrophages (MDM) correlates with an increase in anti-apoptotic (Bcl-2 and Bcl-x(L)) and a decrease in pro-apoptotic (Bax and Bad) proteins. This is associated with macrophage activation as shown by tumor necrosis factor (TNF) production and NF-kappaB activation upon infection. TNF production was shown to be involved in the upregulation of Bcl-2 and Bcl-x(L) because this increase was abolished by an anti-TNF anti-serum or an inhibitor of TNF synthesis. In parallel, inhibition of TNF production induced an increase in the number of apoptotic cells. Furthermore, using an inhibitor of NF-kappaB activation, we demonstrated that TNF-induced upregulation of Bcl-x(L) and Bcl-2 occurs, respectively, through a NF-kappaB-dependent and an NF-kappaB-independent pathway. 相似文献
53.
The effect of surface sugars of liposomes on the immunological responses to entrapped antigen has been investigated. alpha-Mannose and beta-galactose were grafted on the surface of liposomes containing lysozyme by covalent coupling of p-aminophenyl-D-glycosides to phosphatidyl ethanolamine liposomes using glutaraldehyde. Subcutaneous administration of antigen entrapped in beta-galactose liposomes stimulated an antibody response comparable to that elicited by sugar-free neutral liposomes. However, alpha-mannose bearing liposomes with entrapped lysozyme elicited an immune response similar to that induced by lysozyme in saline. Based on these observations it is suggested that alpha-mannose liposomes, that are specifically recognized by macrophages, are taken up rapidly by receptor mediated endocytosis and that the entrapped antigen is then rapidly degraded, resulting in low antibody production. 相似文献
54.
The transmembrane form of TNF-alpha drives autoantibody production in the absence of CD154: studies using MRL/Mp-Fas(lpr) mice 总被引:1,自引:0,他引:1
It is generally accepted that the interaction between CD40 and its ligand (CD154) plays a decisive role in contact-dependent help for T and B cells. In CD154-deficient MRL/Mp-Fas(lpr) (MRL/lpr) mice, however, high titres of IgG2a-type autoantibodies against small nuclear ribonucleoproteins (snRNPs) are observed. We successfully isolated two CD154-deficient MRL/lpr Th1 lines, which could provide B cell help for anti-snRNP antibody production. The proliferative responses of the Th1 cell lines were MHC class II (I-Ek)-restricted. Although syngeneic B cell proliferation was induced by Th1 lines in both a contact-dependent and -independent manner, the soluble form of TNF-alpha (sTNF-alpha) was not involved in contact-independent B cell proliferation. On the other hand, both anti-TNF-alpha and TNF-receptor 2 (TNF-R2, p75) monoclonal antibody (MoAb) blocked contact-dependent B cell proliferation, suggesting that the transmembrane form of TNF-alpha (mTNF-alpha)-TNF-R2 co-stimulation participates in B cell activation. Similarly, anti-TNF-alpha and TNF-R2 MoAb inhibited anti-snRNP antibody production in vitro, but anti-CD154 or TNF-R1 MoAb did not. These results indicate that the interaction of mTNF-alpha on activated Th1 cells with TNF-R2 on B cells may be involved in the autoimmunity seen in MRL mice, and that the blockade of CD40-CD154 co-stimulation may not always be able to suppress some Th1-related manifestations of lupus. 相似文献
55.
56.
Takahashi M Hashimoto H Akizuki M Sasazuki T Nishikimi N Ouchi H Kobayashi Y Numano F Kimura A 《Tissue antigens》2001,57(1):66-69
A polymorphism in high-affinity receptor of TNF (TNFR2) gene, Met196Arg, was reported to be associated with systemic lupus erythematosus (SLE) in Japanese, whereas the association could not be found in Europeans at all and this represents an apparent discrepancy. The association, then, should be tested in other populations to clarify the possible involvement, if any, of the TNFR2 polymorphism in SLE or other related autoimmune diseases. The purposes of this study were to examine the TNFR2 polymorphism in Japanese patients with SLE and to investigate its association with other autoimmune diseases accompanied by vasculitis, mixed connective tissue disease, Buerger's disease, and Takayasu's arteritis. We found no association at all between the TNFR2 polymorphism and any autoimmune diseases including SLE in Japanese. 相似文献
57.
58.
The Thy-1 antigens or rat brain and thymus have been isolated and chemically characterized, but those of mice have not been identified. Moreover, it is uncertain whether the antigens are glycolipids or glycoproteins. This study with highly purified preparations of gangliosides GM1, 1GD1a, GD1b and GT1b from bovine brain and several ganglioside fractions from mouse brain showed that Thy-1 activity does not reside in gangliosides, but rather in the chloroform-methanol-insoluble residue of brain remaining after extraction of gangliosides. The antigen could be solubilized from this residue with a non-ionic detergent. The antigenic activity of the solubilized preparation was heat-labile but resistant to periodate. The chemical properties of the Thy-1 antigen of mouse brain are discussed. 相似文献
59.
Liposomes could bind and fuse efficiently to human erythrocytes in the presence of HVJ when they contained gangliosides isolated from human erythrocytes. Sialosylparagloboside, which has a terminal sequence of NeuAcα2?3Ga1β1?4GlcNac, has a much higher receptor activity to the virus than GD1a, GD1b, GT1b, and GT1a, all of which contain the terminal sequence of NeuAcα2?3Galβ1?3GalNAc or NeuAcα2?8NeuAcα2?3Galβ1?3GalNAc. The activity of sialosylparagloboside is comparable to that of glycophorin, a major sialoglycoprotein of human erythrocytes, when compared on the basis of the required amount (as sialic acid) of compounds. The high affinity of sialosylparagloboside to the viral HANA protein is also suggested by the finding that it showed high inhibitory activity against HVJ-mediated binding of glycophorin liposomes to erythrocytes. Sialosylparagloboside was also highly susceptible to the viral sialidase, the other biological function of HANA protein. 相似文献
60.
The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献