全文获取类型
收费全文 | 568篇 |
免费 | 36篇 |
专业分类
604篇 |
出版年
2023年 | 2篇 |
2022年 | 10篇 |
2021年 | 15篇 |
2020年 | 13篇 |
2019年 | 9篇 |
2018年 | 12篇 |
2017年 | 13篇 |
2016年 | 19篇 |
2015年 | 38篇 |
2014年 | 27篇 |
2013年 | 35篇 |
2012年 | 40篇 |
2011年 | 46篇 |
2010年 | 27篇 |
2009年 | 25篇 |
2008年 | 38篇 |
2007年 | 27篇 |
2006年 | 29篇 |
2005年 | 22篇 |
2004年 | 24篇 |
2003年 | 19篇 |
2002年 | 27篇 |
2001年 | 1篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1968年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有604条查询结果,搜索用时 15 毫秒
71.
72.
Daniela Leite Fabrino Christopher K.E. Bleck Elsa Anes Andrej Hasilik Rossana C.N. Melo Michael Niederweis Gareth Griffiths Maximiliano Gabriel Gutierrez 《Microbes and infection / Institut Pasteur》2009,11(10-11):868-875
Non-pathogenic mycobacteria such us Mycobacterium smegmatis reside in macrophages within phagosomes that fuse with late endocytic/lysosomal compartments. This sequential fusion process is required for the killing of non-pathogenic mycobacteria by macrophages. Porins are proteins that allow the influx of hydrophilic molecules across the mycobacterial outer membrane. Deletion of the porins MspA, MspC and MspD significantly increased survival of M. smegmatis in J774 macrophages. However, the mechanism underlying this observation is unknown. Internalization of wild-type M. smegmatis (SMR5) and the porin triple mutant (ML16) by macrophages was identical indicating that the viability of the porin mutant in vivo was enhanced. This was not due to effects on phagosome trafficking since fusion of phagosomes containing the mutant with late endocytic compartments was unaffected. Moreover, in ML16-infected macrophages, the generation of nitric oxide (NO) was similar to the wild type-infected cells. However, ML16 was significantly more resistant to the effects of NO in vitro compared to SMR5. Our data provide evidence that porins render mycobacteria vulnerable to killing by reactive nitrogen intermediates within phagosomes probably by facilitating uptake of NO across the mycobacterial outer membrane. 相似文献
73.
74.
Katherine A. Mattos Viviane C. G. Oliveira Marcia Berrêdo‐Pinho Julio J. Amaral Luis Caetano M. Antunes Rossana C. N. Melo Chyntia C. D. Acosta Danielle F. Moura Roberta Olmo Jun Han Patricia S. Rosa Patrícia E. Almeida B. Brett Finlay Christoph H. Borchers Euzenir N. Sarno Patricia T. Bozza Georgia C. Atella Maria Cristina V. Pessolani 《Cellular microbiology》2014,16(6):797-815
75.
Linda Sommese Chiara Pagliuca Bice Avallone Rossana Ippolito Amelia Casamassimi Valerio Costa Roberta Colicchio Raimondo Cerciello Maria D'Armiento Margherita Scarpato Alfonso Giovane Gabiria Pastore Teresa Infante Alfredo Ciccodicola Carmela Fiorito Francesco Paolo D'Armiento Paola Salvatore Claudio Napoli 《PloS one》2012,7(11)
Bartonella henselae is able to internalize endothelial progenitor cells (EPCs), which are resistant to the infection of other common pathogens. Bacteroides fragilis is a gram-negative anaerobe belonging to the gut microflora. It protects from experimental colitis induced by Helicobacter hepaticus through the polysaccharide A (PSA). The aim of our study was to establish: 1) whether B. fragilis colonization could protect from B. henselae infection; if this event may have beneficial effects on EPCs, vascular system and tissues. Our in vitro results establish for the first time that B. fragilis can internalize EPCs and competes with B. henselae during coinfection. We observed a marked activation of the inflammatory response by Real-time PCR and ELISA in coinfected cells compared to B. henselae-infected cells (63 vs 23 up-regulated genes), and after EPCs infection with mutant B. fragilis ΔPSA (≅90% up-regulated genes) compared to B. fragilis. Interestingly, in a mouse model of coinfection, morphological and ultrastructural analyses by hematoxylin-eosin staining and electron microscopy on murine tissues revealed that damages induced by B. henselae can be prevented in the coinfection with B. fragilis but not with its mutant B. fragilis ΔPSA. Moreover, immunohistochemistry analysis with anti-Bartonella showed that the number of positive cells per field decreased of at least 50% in the liver (20±4 vs 50±8), aorta (5±1 vs 10±2) and spleen (25±3 vs 40±6) sections of mice coinfected compared to mice infected only with B. henselae. This decrease was less evident in the coinfection with ΔPSA strain (35±6 in the liver, 5±1 in the aorta and 30±5 in the spleen). Finally, B. fragilis colonization was also able to restore the EPC decrease observed in mice infected with B. henselae (0.65 vs 0.06 media). Thus, our data establish that B. fragilis colonization is able to prevent B. henselae damages through PSA. 相似文献
76.
Lucero A. Ramón‐Luing Francisco J. Rendón‐Gandarilla Rosa E. Cárdenas‐Guerra Norma A. Rodríguez‐Cabrera Jaime Ortega‐López Leticia Avila‐González Claudia Angel‐Ortiz Carmen N. Herrera‐Sánchez Manuela Mendoza‐García Rossana Arroyo 《Proteomics》2010,10(3):435-444
Trichomonas vaginalis, a sexually transmitted parasite, has many cysteine proteinases (CPs); some are involved in trichomonal pathogenesis, express during infection, and antibodies against CPs have been detected in patient sera. The goal of this study was to identify the antigenic proteinases of T. vaginalis as potential biomarkers for trichomonosis. The proteases detected when T. vaginalis protein extracts are incubated without protease inhibitors, the trichomonad‐active degradome, and the immunoproteome were obtained by using 2‐DE, 2‐D‐zymograms, 2‐D‐Western blot (WB) assays with trichomonosis patient sera, and MS analysis. Forty‐nine silver‐stained spots were detected in the region of 200–21 kDa of parasite protease‐resistant extracts. A similar proteolytic pattern was observed in the 2‐D zymograms. Nine CPs were identified in the 30 kDa region (TvCP1, TvCP2, TvCP3, TvCP4, TvCP4‐like, TvCP12, TvCPT, TvLEGU‐1, and another legumain‐like CP). The major reactive spots to T. vaginalis‐positive patient sera by 2‐D‐WB corresponded to four papain‐like (TvCP2, TvCP4, TvCP4‐like, TvCPT), and one legumain‐like (TvLEGU‐1) CPs. The genes of TvCP4, TvCPT, and TvLEGU‐1 were cloned, sequenced, and expressed in Escherichia coli. Purified recombinant CPs were recognized by culture‐positive patient sera in 1‐D‐WB assays. These data show that some CPs could be potential biomarkers for serodiagnosis of trichomonosis. 相似文献
77.
Marta Deganuto Laura Cesaratto Cristina Bellarosa Raffaella Calligaris Sandra Vilotti Giovanni Renzone Rossana Foti Andrea Scaloni Stefano Gustincich Franco Quadrifoglio Claudio Tiribelli Gianluca Tell 《Proteomics》2010,10(8):1645-1657
Unconjugated bilirubin (UCB) is a powerful antioxidant and a modulator of cell growth through the interaction with several signal transduction pathways. Although newborns develop a physiological jaundice, in case of severe hyperbilirubinemia UCB may become neurotoxic causing severe long‐term neuronal damages, also known as bilirubin encephalopathy. To investigate the mechanisms of UCB‐induced neuronal toxicity, we used the human neuroblastoma cell line SH‐SY5Y as an in vitro model system. We verified that UCB caused cell death, in part due to oxidative stress, which leads to DNA damage and cell growth reduction. The mechanisms of cytotoxicity and cell adaptation to UCB were studied through a proteomic approach that identified differentially expressed proteins involved in cell proliferation, intracellular trafficking, protein degradation and oxidative stress response. In particular, the results indicated that cells exposed to UCB undertake an adaptive response that involves DJ‐1, a multifunctional neuroprotective protein, crucial for cellular oxidative stress homeostasis. This study sheds light on the mechanisms of bilirubin‐induced neurotoxicity and might help to design a strategy to prevent or ameliorate the neuronal damages leading to bilirubin encephalopathy. 相似文献
78.
Stefano Corsano Giovannella Strappaghetti Rossana Scapicchi Olimpia Scalise 《Bioorganic & medicinal chemistry letters》1993,3(12):2713-2716
The synthesis and evaluaton of the biological activity of a series of 3(2H)-pyridazinones is reported. The bronchodilatating activity of these compounds was determined on the guinea pig trachea. Compounds 6 and 17 with 1-(4-amino-3,5-dichlorophenyl)-2-hydroxyethyl-and 1-(3,4-dichlorophenyl)-2-hydroxyethyl groups linked through a piperazine ring to the 6-position of 3(2H)-pyridazinone show a good bronchospasmolytic activity. 相似文献
79.
80.
Lozano-Alvarez E Briones-Fourzán P Ramírez-Estévez A Placencia-Sánchez D Huchin-Mian JP Rodríguez-Canul R 《Diseases of aquatic organisms》2008,80(2):95-104
Caribbean spiny lobsters Panulirus argus are socially gregarious, preferring shelters harboring conspecifics over empty shelters. In laboratory trials, however, healthy lobsters strongly avoided shelters harboring lobsters infected with the highly pathogenic Panulirus argus Virus 1 (PaV1). Because PaV1 is transmitted by contact, this behavior may thwart its spread in wild lobsters. In a field experiment conducted from 1998 to 2002 in a shelter-poor reef lagoon (Puerto Morelos, Mexico), densities of juvenile P. argus increased significantly on sites enhanced with artificial shelters (casitas) but not on control sites. Because PaV1 emerged in this location during 2000, we reexamined these data to assess whether casitas could potentially increase transmission of PaV1. In 2001, PaV1 prevalence was 2.5% and the cohabitation level (percentage of healthy lobsters cohabiting with diseased lobsters) was similar between natural shelters (3.5%) and casitas (2.4 %). The relative lobster densities in casita sites and control sites did not change significantly before (1998-1999) or after (2001-2002) the disease emergence. In late 2006, data from casita sites showed a significant increase in prevalence (10.9%) and cohabitation level (29.4%), but no significant changes in lobster density. In May 2006, casitas were deployed on shelter-poor sites within Chinchorro Bank, 260 km south of Puerto Morelos. In late 2006, prevalence and cohabitation level were 7.4 and 21.7%, respectively. Our results are inconclusive as to whether or not casitas increase PaV1 transmission, but suggest that across shelter-poor habitats, lobsters make a trade-off between avoiding diseased conspecifics and avoiding predation risk. 相似文献