全文获取类型
收费全文 | 17495篇 |
免费 | 985篇 |
国内免费 | 65篇 |
专业分类
耳鼻咽喉 | 235篇 |
儿科学 | 461篇 |
妇产科学 | 344篇 |
基础医学 | 2548篇 |
口腔科学 | 303篇 |
临床医学 | 1565篇 |
内科学 | 3480篇 |
皮肤病学 | 518篇 |
神经病学 | 2158篇 |
特种医学 | 1049篇 |
外科学 | 2360篇 |
综合类 | 128篇 |
一般理论 | 4篇 |
预防医学 | 886篇 |
眼科学 | 292篇 |
药学 | 950篇 |
中国医学 | 62篇 |
肿瘤学 | 1202篇 |
出版年
2023年 | 149篇 |
2022年 | 244篇 |
2021年 | 438篇 |
2020年 | 294篇 |
2019年 | 415篇 |
2018年 | 449篇 |
2017年 | 402篇 |
2016年 | 501篇 |
2015年 | 497篇 |
2014年 | 689篇 |
2013年 | 823篇 |
2012年 | 1337篇 |
2011年 | 1401篇 |
2010年 | 807篇 |
2009年 | 704篇 |
2008年 | 1166篇 |
2007年 | 1158篇 |
2006年 | 1101篇 |
2005年 | 1094篇 |
2004年 | 933篇 |
2003年 | 883篇 |
2002年 | 796篇 |
2001年 | 158篇 |
2000年 | 129篇 |
1999年 | 173篇 |
1998年 | 190篇 |
1997年 | 137篇 |
1996年 | 140篇 |
1995年 | 90篇 |
1994年 | 94篇 |
1993年 | 66篇 |
1992年 | 55篇 |
1991年 | 56篇 |
1990年 | 43篇 |
1989年 | 28篇 |
1988年 | 40篇 |
1987年 | 34篇 |
1986年 | 36篇 |
1985年 | 35篇 |
1984年 | 30篇 |
1983年 | 22篇 |
1982年 | 31篇 |
1981年 | 23篇 |
1980年 | 35篇 |
1979年 | 25篇 |
1978年 | 21篇 |
1977年 | 31篇 |
1976年 | 18篇 |
1936年 | 15篇 |
1933年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
102.
Christian Stock Birgit Gassner Christof R. Hauck Hannelore Arnold Sabine Mally Johannes A. Eble Peter Dieterich Albrecht Schwab 《The Journal of physiology》2005,567(1):225-238
Their glycolytic metabolism imposes an increased acid load upon tumour cells. The surplus protons are extruded by the Na+ /H+ exchanger (NHE) which causes an extracellular acidification. It is not yet known by what mechanism extracellular pH (pHe ) and NHE activity affect tumour cell migration and thus metastasis. We studied the impact of pHe and NHE activity on the motility of human melanoma (MV3) cells. Cells were seeded on/in collagen I matrices. Migration was monitored employing time lapse video microscopy and then quantified as the movement of the cell centre. Intracellular pH (pHi ) was measured fluorometrically. Cell–matrix interactions were tested in cell adhesion assays and by the displacement of microbeads inside a collagen matrix. Migration depended on the integrin α2β1. Cells reached their maximum motility at pHe ∼7.0. They hardly migrated at pHe 6.6 or 7.5, when NHE was inhibited, or when NHE activity was stimulated by loading cells with propionic acid. These procedures also caused characteristic changes in cell morphology and pHi . The changes in pHi , however, did not account for the changes in morphology and migratory behaviour. Migration and morphology more likely correlate with the strength of cell–matrix interactions. Adhesion was the strongest at pHe 6.6. It weakened at basic pHe , upon NHE inhibition, or upon blockage of the integrin α2β1. We propose that pHe and NHE activity affect migration of human melanoma cells by modulating cell–matrix interactions. Migration is hindered when the interaction is too strong (acidic pHe ) or too weak (alkaline pHe or NHE inhibition). 相似文献
103.
104.
Effect of osteopontin alleles on beta-glucan-induced granuloma formation in the mouse liver 总被引:1,自引:0,他引:1 下载免费PDF全文
Tanaka K Morimoto J Kon S Kimura C Inobe M Diao H Hirschfeld G Weiss JM Uede T 《The American journal of pathology》2004,164(2):567-575
The granuloma formation is a host defense response against persistent irritants. Osteopontin is centrally involved in the formation of granulomas. Three osteopontin alleles, designated a, b, and c, have been found in mice. Here we used a murine model of zymosan (beta-glucan)-induced granuloma formation in the liver to determine possible functional differences between the osteopontin alleles in cell-mediated immunity. In contrast to mice with alleles a or c, mice with the allele b was defective in granuloma formation. As detected by mRNA expression, cytokines and chemokines known to be critically involved in granuloma formation were elicited in liver tissue, regardless of the osteopontin allele expressed. Alignment of the deduced amino acid sequences showed that unlike osteopontin c, b differs from a in 11 amino acids. All three osteopontin alleles had normal cell-binding properties. However, only the b allelic form was defective in the induction of cell migration as tested with dendritic cells. In conclusion, generation of a granulomatous response in mice depends critically on the presence of a functional osteopontin allele. Defective granuloma formation in mice with allele b is likely to be because of an impaired chemotactic function of the osteopontin b protein on immunocompetent cells. 相似文献
105.
Taams LS Vukmanovic-Stejic M Smith J Dunne PJ Fletcher JM Plunkett FJ Ebeling SB Lombardi G Rustin MH Bijlsma JW Lafeber FP Salmon M Akbar AN 《European journal of immunology》2002,32(6):1621-1630
Anergic/suppressive CD4+CD25+ T cells have been proposed to play an important role in the maintenance of peripheral tolerance. Here we demonstrate that in humans these cells suppress proliferation to self antigens, but also to dietary and foreign antigens. The suppressive CD4+CD25+ T cells display a broad usage of the T cell receptor Vbeta repertoire,suggesting that they recognize a wide variety of antigens. They reside in the primed/memory CD4+CD45RO+CD45RB(low) subset and have short telomeres, indicating that these cells have the phenotype of highly differentiated CD4+ T cells that have experienced repeated episodes of antigen-specific stimulation in vivo. This suggests that anergic/suppressive CD4+CD25+ T cells may be generated in the periphery as a consequence of repeated antigenic encounter. This is supported by the observation that highly differentiated CD4+T cells can be induced to become anergic/suppressive when stimulated by antigen presented by non-professional antigen-presenting cells. We suggest that besides being generated in the thymus, CD4+CD25+ regulatory T cells may also be generated in the periphery. This would provide a mechanism for the generation of regulatory cells that induce tolerance to a wide array of antigens that may not be encountered in the thymus. 相似文献
106.
Bogers JJ Chatterjee S Jacobs W Fallon PG Dunne DW Langermans JA Deelder AM Thomas AW Van Marck EA 《Virchows Archiv : an international journal of pathology》2004,445(3):285-291
Adults and children have differences in their susceptibility to schistosomiasis. Whether this age-dependent innate susceptibility influences parasite-caused granulomogenesis is difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. Hepatic and intestinal granuloma formation was observed in both pre-pubescent and adult monkeys. Two distinct stages of granulomas were discerned, the exudative and the productive stage. In the intestine, more granulomas were generated in the colon than in the ileum. In contrast to the adult animals, the juvenile rhesus monkeys had higher numbers of colonic granulomas, these higher numbers being predominantly of the more advanced productive stage. Juvenile animals had a statistically non-significant increased worm burden. These results suggest that juvenile rhesus monkeys have a significantly more intense and advanced colonic response towards entrapped S. mansoni eggs after primary schistosome infections and, thereby, are more susceptible to parasite infection.Research protocols involving non-human primates received ethical clearance by the Institutional Animal Care and Use Committee of the Biomedical Primate Research Centre (Rijswijk, The Netherlands), according to Dutch Law. 相似文献
107.
Marla Gearing Johannes Tigges Hiroshi Mori Suzanne S. Mirra 《Neurobiology of aging》1996,17(6):54-908
Because aged nonhuman primates show β-amyloid (Aβ) deposition in senile plaques and blood vessels similar to that seen in human aging and AD, we used C-terminal specific antibodies to Aβ40 and Aβ42 to investigate Aβ peptide length in the brains of 11 aged rhesus monkeys and a 59-year-old chimpanzee. In contrast to AD, where the earliest and most prominent form of Aβ in senile plaques is Aβ42, in the monkey, Aβ40-positive plaques predominated. The ratio of Aβ4): Aβ42-positive plaques averaged 2.08 in the monkey, as compared to a mean ratio of 0.37 in 68 human AD subjects (p < 0.001). Aβ40 was also more prominent in the chimpanzee than in humans. Possible explanations for these findings include species differences in the cleavage of Aβ from the amyloid precursor protein or in the activity of a putative carboxy peptidase forming Aβ40 from Aβ42 in situ. 相似文献
108.
Embryonic fibroblasts of BALB/Mo mice carrying the endogenous genome of Moloney murine leukemia virus (M-MuLV) in addition to murine type C viruses were fused with Swiss mouse thymocytes, B lymphocytes, macrophages, or embryonic fibroblasts. We wanted to determine whether these cells contained physiological factors involved in induction of the integrated viral genome(s). Fusion with thymocytes and, to a lesser extent, fusion with B lymphocytes induced viral genome expression as demonstrated by the appearance of viral structural protein p30 detected by immunofluorescence. Maximal expression of p30 was observed about 36 hr after the fusion event, using thymocytes from 1- to 2-week-old Swiss mice. This temporary expression of p30 was not accompanied by release of infectious virus. Fusion of BALB/Mo fibroblasts with Swiss mouse macrophages or embryonic fibroblasts led to neither the production of p30 nor the release of detectable infectious virus. These results suggest the existence of thymocyte-specific and possibly B lymphocyte-specific factor(s) involved in the control of expression of integrated viral genome(s). 相似文献
109.
Accumulation of very long-chain fatty acids does not affect mitochondrial function in adrenoleukodystrophy protein deficiency 总被引:2,自引:0,他引:2
Oezen I Rossmanith W Forss-Petter S Kemp S Voigtländer T Moser-Thier K Wanders RJ Bittner RE Berger J 《Human molecular genetics》2005,14(9):1127-1137
X-linked adrenoleukodystrophy (X-ALD, OMIM 300100) is a severe inherited neurodegenerative disease, associated with the accumulation of very long-chain fatty acids (VLCFA). The recent unexpected observation that the accumulation of VLCFA in tissues of the Abcd1-deficient mouse model for X-ALD is not due to a deficiency in VLCFA degradation, led to the hypothesis that mitochondrial abnormalities might contribute to X-ALD pathology. Here, we report that in spite of substantial accumulation of VLCFA in whole muscle homogenates, normal VLCFA levels were detected in mitochondria obtained by organellar fractionation. Polarographic analyses of the respiratory chain as well as enzymatic assays of isolated muscle mitochondria revealed no differences between X-ALD and control mice. Moreover, analysis by electron microscopy, revealed normal size, structure and localization of mitochondria in muscle of both groups. Similar to the results obtained in skeletal muscle, the mitochondrial enzyme activities in brain homogenates of Abcd1-deficient and wild-type animals also did not differ. Finally, studies on mitochondrial oxidative phosphorylation in permeabilized human skin fibroblasts of X-ALD patients and controls revealed no abnormalities. Thus, we conclude that the accumulation of VLCFA per se does not cause mitochondrial abnormalities and vice versa-mitochondrial abnormalities are not responsible for the accumulation of VLCFA in X-ALD mice. 相似文献
110.
Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry 总被引:3,自引:0,他引:3
Yu P Constien R Dear N Katan M Hanke P Bunney TD Kunder S Quintanilla-Martinez L Huffstadt U Schröder A Jones NP Peters T Fuchs H de Angelis MH Nehls M Grosse J Wabnitz P Meyer TP Yasuda K Schiemann M Schneider-Fresenius C Jagla W Russ A Popp A Josephs M Marquardt A Laufs J Schmittwolf C Wagner H Pfeffer K Mudde GC 《Immunity》2005,22(4):451-465
The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype. 相似文献