全文获取类型
收费全文 | 6911篇 |
免费 | 287篇 |
国内免费 | 37篇 |
专业分类
耳鼻咽喉 | 29篇 |
儿科学 | 137篇 |
妇产科学 | 55篇 |
基础医学 | 828篇 |
口腔科学 | 83篇 |
临床医学 | 497篇 |
内科学 | 1842篇 |
皮肤病学 | 176篇 |
神经病学 | 434篇 |
特种医学 | 400篇 |
外科学 | 1195篇 |
综合类 | 16篇 |
预防医学 | 206篇 |
眼科学 | 101篇 |
药学 | 501篇 |
中国医学 | 37篇 |
肿瘤学 | 698篇 |
出版年
2022年 | 29篇 |
2021年 | 97篇 |
2020年 | 60篇 |
2019年 | 86篇 |
2018年 | 92篇 |
2017年 | 89篇 |
2016年 | 103篇 |
2015年 | 101篇 |
2014年 | 144篇 |
2013年 | 191篇 |
2012年 | 308篇 |
2011年 | 336篇 |
2010年 | 169篇 |
2009年 | 165篇 |
2008年 | 271篇 |
2007年 | 337篇 |
2006年 | 318篇 |
2005年 | 366篇 |
2004年 | 388篇 |
2003年 | 394篇 |
2002年 | 342篇 |
2001年 | 315篇 |
2000年 | 336篇 |
1999年 | 305篇 |
1998年 | 82篇 |
1997年 | 65篇 |
1996年 | 48篇 |
1995年 | 37篇 |
1994年 | 34篇 |
1993年 | 40篇 |
1992年 | 138篇 |
1991年 | 134篇 |
1990年 | 150篇 |
1989年 | 128篇 |
1988年 | 127篇 |
1987年 | 108篇 |
1986年 | 107篇 |
1985年 | 104篇 |
1984年 | 58篇 |
1983年 | 76篇 |
1982年 | 23篇 |
1981年 | 21篇 |
1979年 | 57篇 |
1978年 | 35篇 |
1975年 | 34篇 |
1974年 | 27篇 |
1971年 | 23篇 |
1970年 | 33篇 |
1969年 | 22篇 |
1968年 | 22篇 |
排序方式: 共有7235条查询结果,搜索用时 281 毫秒
51.
Pathogenic mechanism of mouse brain damage caused by oral infection with Shiga toxin-producing Escherichia coli O157:H7 下载免费PDF全文
Kita E Yunou Y Kurioka T Harada H Yoshikawa S Mikasa K Higashi N 《Infection and immunity》2000,68(3):1207-1214
In a previous study, we showed that infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7 (strain Sm(r)N-9) caused neurologic symptoms in malnourished mice with positive immunoreactions of Stx2 in brain tissues. The present study explores the mechanism of how Stx injures the vascular endothelium to enter the central nervous system in mice. Oral infection with strain Sm(r)N-9 elicited a tumor necrosis factor alpha (TNF-alpha) response in the blood as early as 2 days after infection, while Stx was first detected at 3 days postinfection. In the brain, TNF-alpha was detected at day 3, and its quantity was increased over the next 3 days. Frozen sections of the brains from moribound mice contained high numbers of apoptotic cells. Glycolipids recognized by an anti-Gb3 monoclonal antibody were extracted from the brain, and purified Stx2 was able to bind to the glycolipids. In human umbilical vascular endothelial cells (HUVEC) cultured with fluorescein-labeled Stx2 (100 ng/ml), TNF-alpha (20 U/ml) significantly facilitated the intracellular compartmentalization of fluorescence during 24 h of incubation, suggesting the enhanced intracellular processing of Stx2. Consequently, higher levels of apoptosis in HUVEC were found at 48 h. Short-term exposure of HUVEC to Stx2 abrogated their apoptotic response to subsequent incubation with TNF-alpha alone or TNF-alpha and Stx2. In contrast, primary exposure of HUVEC to TNF-alpha followed by exposure to Stx2 alone or TNF-alpha and Stx2 induced apoptosis at the same level as obtained after 48-h incubation with these two agents. These results suggest that the rapid production of circulating TNF-alpha after infection induces a state of competence in vascular endothelial cells to undergo apoptosis, which would be finally achieved by subsequent elevation of Stx in the blood. In this synergistic action, target cells must be first exposed to TNF-alpha. Such cell injury may be a prerequisite to brain damage after infection with Stx-producing E. coli O157:H7. 相似文献
52.
Two infants (4 and 5 months of age) with a febrile episode for 3 and 5 days, respectively, developed skin rashes after the fever subsided and were diagnosed as exanthem subitum. The rash continued for 5 days followed by mild-to-moderate pigmentation. Human herpesvirus-6 and measles virus, which were confirmed by a specific immunofluorescence assay and by electron microscopy, were isolated simultaneously from blood in the acute stage of the disease but not from the convalescent stage. The titer of the herpesvirus-6 in blood was greater than that of measles. Specific serologic assays showed marked seroconversion against human herpesvirus-6 but not to measles virus. The results suggest that dual infection with human herpesvirus-6 and measles virus results in atypical exanthem subitum or modified measles with unique immunologic responses. 相似文献
53.
Construction and characterization of a fimA mutant of Porphyromonas gingivalis. 总被引:4,自引:12,他引:4 下载免费PDF全文
N Hamada K Watanabe C Sasakawa M Yoshikawa F Yoshimura T Umemoto 《Infection and immunity》1994,62(5):1696-1704
Although fimbriae of Porphyromonas gingivalis have been implicated as playing a major role in adherence to gingival tissue surfaces, no conclusive genetic evidence has yet been obtained. The fimA gene, the determinant for the major fimbrial subunit protein, was cloned and sequenced (D. P. Dickinson, M. A. Kubiniec, F. Yoshimura, and R. J. Genco, J. Bacteriol. 170:1658-1665, 1988). We undertook to inactivate the fimA gene by a homologous recombination technique and examined the fimA mutant for changes in surface properties, including production of fimbriae, adherence to human gingival fibroblasts and epithelial cells, hemagglutinating activity, and surface hydrophobicity. To inactivate the fimA gene, we disrupted a fimA clone by insertion of a DNA segment containing an erythromycin resistance (Emr) gene. This was then delivered into P. gingivalis ATCC 33277 from an Escherichia coli K-12 strain, SM10 lambda pir, by using a mobilizable suicide vector, pGP704; recombination at the fimA locus led to the isolation of a fimA mutant. Disruption of the fimA locus and disappearance of FimA production were confirmed by Southern hybridization with a fimA-specific DNA probe and Western immunoblotting with a monoclonal antibody against the FimA protein, respectively. The fimA mutant constructed failed to express long (0.5- to 1.0-micron) fimbriae from the bacterial surface and had a diminished adhesive capacity to tissue-cultured human gingival fibroblasts and epithelial cells. Observation of the bacteria adhering to human gingival fibroblasts by scanning electron microscopy revealed that the wild-type strain had dramatic local changes in the appearance of the microvilli at the point of contact with large bacterial clumps, whereas the fimA mutant did not. In contrast, neither the hemagglutinating activity nor the surface hydrophobicity was changed in the fimA mutant. These data thus constitute the first direct genetic evidence demonstrating that the FimA protein of P. gingivalis is essential for the interaction of the organism with human gingival tissue cells through a function(s) encoded by the fimA gene. 相似文献
54.
Natsuo Yasui Keiichi Ozono Masayo Yamagata Hidehiko Kawabata Hideki Yoshikawa 《American journal of medical genetics. Part A》2001,99(4):328-330
A 23‐year‐old man was diagnosed as having X‐linked spondyloepiphyseal dysplasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterior hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5′ untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mutation was present in the proband and his unaffected mother (a heterozygote), but not in an unaffected sister and an unaffected uncle. The nature of the mutation predicted that the SEDL protein (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused SEDT. © 2001 Wiley‐Liss, Inc. 相似文献
55.
Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis 下载免费PDF全文
Kwon J Wang YL Setsuie R Sekiguchi S Sato Y Sakurai M Noda M Aoki S Yoshikawa Y Wada K 《The American journal of pathology》2004,165(4):1367-1374
The experimentally induced cryptorchid mouse model is useful for elucidating the in vivo molecular mechanism of germ cell apoptosis. Apoptosis, in general, is thought to be partly regulated by the ubiquitin-proteasome system. Here, we analyzed the function of two closely related members of the ubiquitin C-terminal hydrolase (UCH) family in testicular germ cell apoptosis experimentally induced by cryptorchidism. The two enzymes, UCH-L1 and UCH-L3, deubiquitinate ubiquitin-protein conjugates and control the cellular balance of ubiquitin. The testes of gracile axonal dystrophy (gad) mice, which lack UCH-L1, were resistant to cryptorchid stress-related injury and had reduced ubiquitin levels. The level of both anti-apoptotic (Bcl-2 family and XIAP) and prosurvival (pCREB and BDNF) proteins was significantly higher in gad mice after cryptorchid stress. In contrast, Uchl3 knockout mice showed profound testicular atrophy and apoptotic germ cell loss after cryptorchid injury. Ubiquitin level was not significantly different between wild-type and Uchl3 knockout mice, whereas the levels of Nedd8 and the apoptotic proteins p53, Bax, and caspase3 were elevated in Uchl3 knockout mice. These results demonstrate that UCH-L1 and UCH-L3 function differentially to regulate the cellular levels of anti-apoptotic, prosurvival, and apoptotic proteins during testicular germ cell apoptosis. 相似文献
56.
Human marrow cells-derived cultured bone in porous ceramics 总被引:9,自引:0,他引:9
Yoshikawa T Ohgushi H Uemura T Nakajima H Ichijima K Tamai S Tateisi T 《Bio-medical materials and engineering》1998,8(5-6):311-320
From four patients (mean age, 60 years; range 51-76 years), 3 ml of bone marrow was collected from the ilium. The marrow was cultured to concentrate and expand the marrow mesenchymal cells on a culture dish. The cultured cells were then subcultured either on another culture dish or in porous areas of hydroxyapatite ceramics in the presence of dexamethasone and beta-glycerophosphate (osteogenic medium). The subcultured tissues on the dishes were analyzed by scanning electron microscopy (SEM), and subcultured tissues in the ceramics were implanted intraperitoneally into athymic nude mice. Vigorous growth of spindle-shaped cells and a marked formation of bone matrix beneath the cell layers was observed on the subculture dishes by SEM. The intraperitoneally implanted ceramics with cultured tissues revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the ceramics after 2 months. The in vitro bone formation on the culture dishes and in vivo bone formation in porous ceramics were detected in all cases. These results indicate that we can assemble an in vitro bone/ceramic construct, and due to the porous framework of the ceramic, the construct has osteogenic potential similar to that of autologous cancellous bone. A significant benefit of this method is that the construct can be made with only a small amount of aspirated marrow cells from aged patients with little host morbidity. 相似文献
57.
Pathogenesis of Rinderpest Virus Infection in Rabbits II. Effect of Rinderpest Virus on the Immune Functions of Rabbits 下载免费PDF全文
Kazuya Yamanouchi Akiko Fukuda Fumio Kobune Yasuhiro Yoshikawa Fumitoshi Chino 《Infection and immunity》1974,9(2):206-211
Rinderpest virus infection was shown to induce marked suppression of both humoral antibody response and cell-mediated immunity in rabbits. The virus exhibited a suppressive effect on primary antibody response as indicated by a decrease in numbers of plaque-forming cells (immunoglobulin [Ig]M) and hemagglutinating antibody titers of both IgM and IgG types to sheep red blood cells, whereas there was no detectable effect of the virus on the production of memory cells. Virus-induced suppression of cell-mediated immunity was demonstrated by a decreased rate of proliferative response of peripheral lymphocytes to phytohemagglutinin stimulus and by a depression of delayed-type skin reactions to purified protein derivative. Such suppressive effects were indicated to persist for 14 days or longer. Alteration in phagocytic activity of the reticuloendothelial system was not observed. The relevance of the virus-induced histological lesions in the lymphoid tissues to the virus-induced immunosuppression was discussed. 相似文献
58.
Interaction of cholecystokinin (CCK) with vasoactive intestinal peptide (VIP) in body shaking response to ice-water immersion was observed in pentobarbital-anesthetized rats. Although CCK itself had no influence on the response, VIP suppressed it and this effect of VIP was antagonized by simultaneous administration of sulfated octapeptide of CCK, but not by non-sulfated CCK. 相似文献
59.
Susumu Yoshikawa Jitsuo Kiji Junji Furukawa 《Macromolecular chemistry and physics.》1977,178(4):1077-1087
The dimerization of 1-alkynes by rhodium(I) complexes in the presence of phosphorus ligands is described. The products are linear and branched dimers, the ratio of which is correlated with the electronic parameters, vCO of Ni(CO)3L, of the ligands L, but no simple correlation is apparent between their steric parameter and the selectivity. Electron-donating ligands promote the formation of the linear dimer. The substituents of the 1-alkynes also affect the distribution of linear and branched dimers. Electron-donating substituents prefer linear isomer to branched one. The reactivity of the substituted 1-alkynes (R? C?C? H) increased with substituent R in the order 相似文献
60.
The morphology of the equine allantochorion at the tip of the pregnant horn was studied in the membranes of 14 mares. The findings in the allantochorion at the tip of the pregnant horn were of two types; one was growth retardation (hypoplastic villi, tunica adventitia of the vessels resembling embryonal connective tissue and the extended spaces of remnants of the extraembryonic coelom), the other was placental hypoxia or ischaemia (parakeratosis, stratified squamous metaplasia, necrosis of the trophoblasts, thickening of the basement membrane and fibrous hyperplasia of villous stroma). It seems likely that hypoplastic villi are caused by disordered formation of the microcotyledon accompanying the progression of pregnancy. 相似文献