全文获取类型
收费全文 | 516篇 |
免费 | 40篇 |
国内免费 | 19篇 |
专业分类
儿科学 | 35篇 |
妇产科学 | 11篇 |
基础医学 | 85篇 |
口腔科学 | 8篇 |
临床医学 | 64篇 |
内科学 | 111篇 |
皮肤病学 | 15篇 |
神经病学 | 14篇 |
特种医学 | 112篇 |
外科学 | 40篇 |
综合类 | 11篇 |
预防医学 | 20篇 |
眼科学 | 9篇 |
药学 | 16篇 |
中国医学 | 2篇 |
肿瘤学 | 22篇 |
出版年
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 13篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 8篇 |
2014年 | 15篇 |
2013年 | 15篇 |
2012年 | 12篇 |
2011年 | 17篇 |
2010年 | 16篇 |
2009年 | 23篇 |
2008年 | 15篇 |
2007年 | 19篇 |
2006年 | 9篇 |
2005年 | 13篇 |
2004年 | 8篇 |
2003年 | 10篇 |
2002年 | 7篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 15篇 |
1998年 | 34篇 |
1997年 | 42篇 |
1996年 | 30篇 |
1995年 | 20篇 |
1994年 | 18篇 |
1993年 | 18篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 15篇 |
1989年 | 21篇 |
1988年 | 13篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1980年 | 11篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1968年 | 1篇 |
1946年 | 1篇 |
1941年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有575条查询结果,搜索用时 0 毫秒
1.
The human visual system is amenable to a number of adaptive processes; one such process, or collection of processes, is the adaptation to blur. Blur adaptation can be observed as an improvement in vision under degraded conditions, and these changes occur relatively rapidly following exposure to blur. The potential important future directions of this research area and the clinical implications of blur adaptation are discussed. 相似文献
2.
Hausegger KA; Cragg AH; Lammer J; Lafer M; Fluckiger F; Klein GE; Sternthal MH; Pilger E 《Radiology》1994,190(1):199
3.
Focal liver lesions: characterization with triphasic spiral CT 总被引:15,自引:1,他引:14
4.
Metabolic adaptation of the chick embryo to chronic hypoxia 总被引:1,自引:0,他引:1
5.
6.
R. T. Hayden J. R. Uhl X. Qian M. K. Hopkins M. C. Aubry A. H. Limper R. V. Lloyd F. R. Cockerill 《Journal of clinical microbiology》2001,39(7):2618-2626
We developed a rapid thermocycling, real-time detection (also known as real-time PCR) method for the detection of Legionella species directly from clinical specimens. This method uses the LightCycler (Roche Molecular Biochemicals, Indianapolis, Ind.) and requires approximately 1 to 2 h to perform. Both a Legionella genus PCR assay and Legionella pneumophila species-specific PCR assay were designed. A total of 43 archived specimens from 35 patients were evaluated, including 19 bronchoalveolar lavage (BAL) specimens and 24 formalin-fixed, paraffin-embedded open lung biopsy specimens. Twenty-five of the specimens were culture-positive for Legionella (9 BAL specimens and 16 tissue specimens). BAL specimens were tested by LightCycler PCR (LC-PCR) methods and by a direct fluorescent antibody (DFA) assay, which detects L. pneumophila serogroups 1 to 6 and several other Legionella species. Tissue sections were tested by the two LC-PCR methods, by DFA, by an in situ hybridization (ISH) assay, specifically designed to detect L. pneumophila, and by Warthin-Starry (WS) staining. The results were compared to the "gold standard" method of bacterial culture. With BAL specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by Legionella genus LC-PCR, 100 and 100%; Legionella genus detection by DFA assay, 33 and 100%; and L. pneumophila detection by L. pneumophila species-specific LC-PCR, 100 and 100%. With open lung biopsy specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by LC-PCR 68.8 and 100%; Legionella genus detection by DFA assay, 44 and 100%; Legionella genus detection by WS staining, 63 and 100%; L. pneumophila species-specific detection by LC-PCR, 17 and 100%; and L. pneumophila species-specific detection by ISH, 100 and 100%. The analytical sensitivity of both LC-PCR assays was <10 CFU/reaction. LC-PCR is a reliable method for the direct detection of Legionella species from BAL specimens. The Legionella genus LC-PCR assay could be performed initially; if positive, L. pneumophila species-specific LC-PCR could then be performed (if species differentiation is desired). The speed with which the LC-PCR procedure can be performed offers significant advantages over both culture-based methods and conventional PCR techniques. In contrast, for the methods evaluated, culture was the best for detecting multiple Legionella species in lung tissue. WS staining, Legionella genus LC-PCR, and L. pneumophila species-specific ISH were useful as rapid tests with lung tissue. 相似文献
7.
Lung epithelial cells and extracellular matrix components induce expression of Pneumocystis carinii STE20, a gene complementing the mating and pseudohyphal growth defects of STE20 mutant yeast
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pneumocystis carinii causes severe pneumonia in immunocompromised hosts. The binding of P. carinii to alveolar epithelial cells and extracellular matrix constituents such as fibronectin and vitronectin is a central feature of infection, which initiates proliferation of the organism. Herein, we demonstrate that P. carinii binding to lung cells specifically alters the gene expression of the organism, regulating fungal growth. Subtractive hybridization was performed to isolate P. carinii genes expressed following binding to mammalian extracellular matrix constituents. P. carinii STE20 (PCSTE20), a gene participating in mating and pseudohyphal growth of other fungi, was identified following adherence to the extracellular matrix constituents fibronectin, vitronectin, collagen, and lung epithelial cells. The expression of PCSTE20 and a related P. carinii mitogen-activated protein kinase (MAPK) kinase gene, also implicated in signaling of mating, were both specifically upregulated by binding to matrix protein. The expression of general cyclin-dependent kinases and other MAPKs not involved in mating pathways were not altered by organism binding. PCSTE20 expression was also strongly enhanced following organism attachment to A549 lung epithelial cells. When expressed in a Saccharomyces cerevisiae ste20Delta mutant, PCSTE20 suppressed defects in both mating and pseudohyphal growth. These findings are consistent with the observed proliferation and filopodial extension of Pneumocystis organisms adherent to the epithelium in the lungs of immunocompromised hosts. PCSTE20 expression appears to represent a significant component in the regulation of the life cycle of this intractable opportunistic pathogen. 相似文献
8.
Vitronectin binds to Pneumocystis carinii and mediates organism attachment to cultured lung epithelial cells. 总被引:6,自引:5,他引:6
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A H Limper J E Standing O A Hoffman M Castro L W Neese 《Infection and immunity》1993,61(10):4302-4309
Pneumocystis carinii attaches to alveolar epithelial cells during the development of pneumonia. Adhesive proteins found within the alveolar space have been proposed to mediate P. carinii adherence to lung cells. Vitronectin (Vn), a 75-kDa glycoprotein present in the lower respiratory tract, has substantial cell-adhesive properties and might participate in the host-parasite interaction during P. carinii pneumonia. To address whether Vn binds to P. carinii, we studied the interaction of radiolabeled Vn with purified P. carinii organisms. Vn bound to P. carinii, occupying an estimated 5.47 x 10(5) binding sites per organism, with an affinity constant, Kd, of 4.24 x 10(-7) M. Interestingly, the interaction of Vn with P. carinii was not mediated through the Arg-Gly-Asp cell-adhesive domain of Vn. Addition of Arg-Gly-Asp-Ser (RGDS) peptides did not inhibit binding. In contrast, Vn binding to P. carinii was substantially inhibited by the addition of heparin or by digesting the organisms with heparitinase, suggesting that P. carinii may interact with the glycosaminoglycan-binding domain of Vn. To determine whether Vn might enhance P. carinii attachment to lung epithelial cells, we studied the binding of 51Cr-labeled P. carinii to cultured A549 lung cells. Addition of Vn resulted in significantly increased binding of P. carinii to A549 cells, whereas a neutralizing anti-Vn serum substantially reduced the binding of P. carinii to A549 cells. These data suggest that Vn binds to P. carinii and that Vn might provide an additional means by which P. carinii attaches to respiratory epithelial cells. 相似文献
9.
The aim of this study was to detect the surface antigens in different stages of experimental induced Pneumocystis carinii in Sprague-Dawley rats. Immunohistochemical staining with monoclonal (900, 902 and 904) and polyclonal (SP-D) antibodies demonstrated that the P. carinii organisms were mostly in the alveolar lumina. The binding sites of the monoclonal (900, 902 and 904) and polyclonal (SP-D) antibodies developed against P. carinii were examined at the ultrastructural level by using a post-embedding immunogold labeling. The gold particles were observed evenly on the surface of precyst and cyst stages of the P. carinii. In the trophozoite stage, scattered gold particles were seen on the pellicles and tubular expansions. The monoclonal antibodies reacted mainly with pellicles of P. carinii, whereas SP-D labeled pellicles, intracystic bodies, cytoplasms of alveolar macrophages, free floating surfactant material in the alveolar spaces, and adjacent type II epithelial cells. In the immunogold labeling, basically no significant differences were found in the precyst, cyst, and ruptured cyst stages. These results indicate that the gold particles were observed adhering to every stage of P. carinii, mostly concentrated on the pellicles, and more concentrated in the precyst or cyst stage than trophozoite stage which may be due to an increase in antigen accumulation during development from the trophozoite to the cyst. 相似文献
10.
Candida albicans stimulates arachidonic acid liberation from alveolar macrophages through alpha-mannan and beta-glucan cell wall components. 总被引:3,自引:3,他引:3
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M Castro N V Ralston T I Morgenthaler M S Rohrbach A H Limper 《Infection and immunity》1994,62(8):3138-3145
Candida albicans is an increasingly important fungal pathogen. Alveolar macrophages respond to fungal components such as zymosan by releasing arachidonic acid (AA) and AA metabolites. However, few studies hypothesized that macrophages respond to C. albicans by releasing AA and generating AA metabolites as a consequence of interaction of mannose and beta-glucan receptors with fungal cell wall components. [14C]AA-labeled rabbit alveolar macrophages released AA following stimulation with either live or heat-killed C. albicans. High-pressure liquid chromatography analysis revealed that 55% of the AA released was metabolized via cyclooxygenase and lipoxygenase pathways. The metabolites consisted of prostaglandin E2, prostaglandin F2 alpha, 6-ketoprostaglandin F1 alpha, thromboxane B2, and leukotrienes B4 and D4. We further examined the roles of alpha-mannan and beta-glucan components of C. albicans in mediating these alterations of eicosanoid metabolism. Prior work in our laboratory has shown that soluble alpha-mannan and beta-glucan inhibit macrophage mannose and beta-glucan receptors, respectively. Incubation of alveolar macrophages with soluble alpha-mannan derived from C. albicans (1 mg/ml) resulted in 49.8% +/- 2.6% inhibition of macrophage AA release during stimulation with intact C. albicans (P = 0.0001 versus control). Macrophage AA release in response to C. albicans was also inhibited to a significant but lesser degree by soluble beta-glucan (36.2% +/- 1.3%; P = 0.008 versus control). These results indicate that C. albicans stimulates macrophage AA metabolism and that these effects are partly mediated by alpha-mannan and beta-glucan constituents of the fungus. 相似文献