全文获取类型
收费全文 | 328篇 |
免费 | 45篇 |
出版年
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2016年 | 8篇 |
2015年 | 17篇 |
2014年 | 12篇 |
2013年 | 18篇 |
2012年 | 21篇 |
2011年 | 23篇 |
2010年 | 5篇 |
2009年 | 15篇 |
2008年 | 12篇 |
2007年 | 11篇 |
2006年 | 11篇 |
2005年 | 11篇 |
2004年 | 15篇 |
2003年 | 9篇 |
2002年 | 24篇 |
2001年 | 8篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 9篇 |
1991年 | 12篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 10篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1963年 | 2篇 |
1962年 | 2篇 |
1957年 | 1篇 |
排序方式: 共有373条查询结果,搜索用时 15 毫秒
111.
Bozza S Fallarino F Pitzurra L Zelante T Montagnoli C Bellocchio S Mosci P Vacca C Puccetti P Romani L 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(5):2910-2918
By mediating tryptophan catabolism, the enzyme indoleamine 2,3-dioxygenase (IDO) has a complex role in immunoregulation in infection, pregnancy, autoimmunity, transplantation, and neoplasia. We hypothesized that IDO might affect the outcome of the infection in mice infected with Candida albicans by virtue of its potent regulatory effects on inflammatory and T cell responses. IDO expression was examined in mice challenged with the fungus along with the consequences of its blockade by in vivo treatment with an enzyme inhibitor. We found that IDO activity was induced at sites of infection as well as in dendritic cells and effector neutrophils via IFN-gamma- and CTLA-4-dependent mechanisms. IDO inhibition greatly exacerbated infection and associated inflammatory pathology as a result of deregulated innate and adaptive/regulatory immune responses. However, a role for tryptophan catabolism was also demonstrated in a fungus-autonomous fashion; its blockade in vitro promoted yeast-to-hyphal transition. These results provide novel mechanistic insights into complex events that, occurring at the fungus/pathogen interface, relate to the dynamics of host adaptation to the fungus. The production of IFN-gamma may be squarely placed at this interface, where IDO activation probably exerts a fine control over fungal morphology as well as inflammatory and adaptive antifungal responses. 相似文献
112.
Production of IL-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by IL-4 总被引:19,自引:0,他引:19
Ebner S Ratzinger G Krösbacher B Schmuth M Weiss A Reider D Kroczek RA Herold M Heufler C Fritsch P Romani N 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(1):633-641
Dendritic cells produce IL-12 both in response to microbial stimuli and to T cells, and can thus skew T cell reactivity toward a Th1 pattern. We investigated the capacity of dendritic cells to elaborate IL-12 with special regard to their state of maturation, different maturation stimuli, and its regulation by Th1/Th2-influencing cytokines. Monocyte-derived dendritic cells were generated with GM-CSF and IL-4 for 7 days, followed by another 3 days +/- monocyte-conditioned media, yielding mature (CD83(+)/dendritic cell-lysosome-associated membrane glycoprotein(+)) and immature (CD83(-)/dendritic cell-lysosome-associated membrane glycoprotein(-)) dendritic cells. These dendritic cells were stimulated for another 48 h, and IL-12 p70 was measured by ELISA. We found the following: 1) Immature dendritic cells stimulated with CD154/CD40 ligand or bacteria (both of which concurrently also induced maturation) secreted always more IL-12 than already mature dendritic cells. Mature CD154-stimulated dendritic cells still made significant levels (up to 4 ng/ml). 2) Terminally mature skin-derived dendritic cells did not make any IL-12 in response to these stimuli. 3) Appropriate maturation stimuli are required for IL-12 production: CD40 ligation and bacteria are sufficient; monocyte-conditioned media are not. 4) Unexpectedly, IL-4 markedly increased the amount of IL-12 produced by both immature and mature dendritic cells, when present during stimulation. 5) IL-10 inhibited the production of IL-12. Our results, employing a cell culture system that is now being widely used in immunotherapy, extend prior data that IL-12 is produced most abundantly by dendritic cells that are beginning to respond to maturation stimuli. Surprisingly, IL-12 is only elicited by select maturation stimuli, but can be markedly enhanced by the addition of the Th2 cytokine, IL-4. 相似文献
113.
114.
Robledo R Orru S Sidoti A Muresu R Esposito D Grimaldi MC Carcassi C Rinaldi A Bernini L Contu L Romani M Roe B Siniscalco M 《Genomics》2002,80(6):585-592
We show a mute 9.1-kb gap in the human genome reference map, unraveled by RDA studies, to be a worldwide deletion/insertion polymorphism of stable type. The molecular and population data presented suggest its origin from a unique ancestral transposition event in chromosomal region 22q11.2, overlapping the IglambdaV genes at about 450 kb from the cluster of the IglambdaJ-C genes. These findings are not meant to be just another report of a polymorphic marker suitable for population studies. Rather, we wish to stress that a large number of inborn mute gaps may be spread all over the genome and that the many RDA-detected microdeletions already available are efficient tools for the discovery of this otherwise hidden category of genetic variation. Apart from their possible impact on expression of structural genes, mute gaps must be filled for the reference map of our genome to be truly completed. 相似文献
115.
Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): differential intracellular fate of virions in mature and immature DCs 下载免费PDF全文
Frank I Piatak M Stoessel H Romani N Bonnyay D Lifson JD Pope M 《Journal of virology》2002,76(6):2936-2951
As potential targets for human immunodeficiency virus type 1 and simian immunodeficiency virus (HIV-1 and SIV), dendritic cells (DCs) likely play a significant role in the onset and spread of infection as well as in the induction of antiviral immunity. Using the SIV-macaque system to study the very early events in DC-virus interactions, we compared chemically inactivated SIV having conformationally and functionally intact envelope glycoproteins (2,2'-dithiodipyridine [AT-2] SIV) to infectious and heat-treated SIV. Both human and macaque DCs interact similarly with SIV without detectable effects on DC viability, phenotype, or endocytic function. As assessed by measuring cell-associated viral RNA, considerable amounts of virus are captured by the DCs and this is reduced when the virus is heat treated or derived from a strain that expresses low levels of envelope glycoprotein. Immunostaining for SIV proteins and electron microscopy indicated that few intact virus particles are retained at the periphery of the endocytically active, immature DCs. This contrasts with a perinuclear localization of numerous virions in large vesicular compartments deeper within mature DCs (in which macropinocytosis is down-regulated). Both immature and mature DCs are capable of clathrin-coated pit-mediated uptake of SIV, supporting the notion that the receptor-mediated uptake of virus can occur readily in mature DCs. While large numbers of whole viruses were preferentially found in mature DCs, both immature and mature DCs contained similar amounts of viral RNA, suggesting that different uptake/virus entry mechanisms are active in immature and mature DCs. These findings have significant implications for cell-to-cell transmission of HIV-1 and SIV and support the use of AT-2 SIV, an authentic but noninfectious form of virus, as a useful tool for studies of processing and presentation of AT-2 SIV antigens by DCs. 相似文献
116.
The addition of norepinephrine to perfused rat livers and to collagenase isolated hepatocytes induced a marked and dose-dependent magnesium efflux. The addition of beta-adrenergic receptor antagonists, but not alpha-antagonists, completely blocked the Mg2+ efflux. The Mg2+ efflux could also be induced by forskolin and by permeable cAMP analogues. By contrast, the addition of carbachol or vasopressin induced a Mg2+ influx into isolated hepatocytes. These results indicate that a significant Mg2+ efflux from liver cells can be induced through the beta-adrenergic receptors and that it is mediated through the cytosolic cAMP levels. 相似文献
117.
T cell subsets and IFN-gamma production in resistance to systemic candidosis in immunized mice 总被引:12,自引:0,他引:12
E Cenci L Romani A Vecchiarelli P Puccetti F Bistoni 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(11):4333-4339
In addition to previous evidence for the roles of T cell-dependent immunity and delayed-type hypersensitivity in acquired resistance to systemic candidosis in mice, in the present study we have investigated the relative contributions of L3T4+ and Lyt-2+ lymphocytes in the protective immunity induced by vaccination with low virulence Candida albicans cells. We have also addressed the issue of the mode of Candida Ag recognition by specific T cells leading to cytokine release. Spleen cells from immunized mice produced high levels of IFN-gamma in vitro in response to Candida Ag, and this activity was abolished only by the combined treatment of the responder population with anti-L3T4 and anti-Lyt-2.2 mAb plus C. Positively selected L3T4+ and Lyt-2+ cells also produced IFN-gamma in vitro, provided accessory cells (plastic-adherent and Thy-1- Ia- splenocytes, respectively) were added to the lymphocyte-yeast cell cocultures. The production of IFN-gamma by purified L3T4+ and Lyt-2+ cells was inhibited by addition of the respective anti-class II and anti-class I H-2 antibody to the cultures. In vivo, administration of anti-L3T4, anti-Lyt-2.2 mAb or a combination of both significantly impaired the resistance of immunized mice to challenge with virulent C. albicans, as manifested by increased recovery of the yeast from the mouse kidneys. A similar effect was observed upon neutralization of endogenous IFN-gamma by treatment with rat mAb. These results suggest that both L3T4+ and Lyt-2+ T cells play a role in acquired immunity to systemic C. albicans infection, and that their activity may involve IFN-gamma-mediated stimulation of candidacidal mechanisms. 相似文献
118.
Marta Romani Francesca Mancini Alessia Micalizzi Andrea Poretti Elide Miccinilli Patrizia Accorsi Emanuela Avola Enrico Bertini Renato Borgatti Romina Romaniello Serdar Ceylaner Giangennaro Coppola Stefano D’Arrigo Lucio Giordano Andreas R. Janecke Mario Lituania Kathrin Ludwig Loreto Martorell Tommaso Mazza Sylvie Odent Lorenzo Pinelli Pilar Poo Margherita Santucci Sabrina Signorini Alessandro Simonati Ronen Spiegel Franco Stanzial Maja Steinlin Brahim Tabarki Nicole I. Wolf Federica Zibordi Eugen Boltshauser Enza Maria Valente 《Human genetics》2015,134(1):123-126
119.
A cytogenetic analysis of twenty cases of systemic scleroderma 总被引:1,自引:0,他引:1
Cytogenetic studies were performed on 20 patients with diffuse scleroderma who had not received recent or high doses of irradiation; 1,267 cells were examined. Neither the culture medium composition nor the disease had any significant effect on the frequency of structural chromatidic or chromosomal abnormalities. 相似文献
120.
Laura?Fancellu Walter?Borsini Ilaria?Romani Angelo?Pirisi Giovanni?Andrea?Deiana Elia?Sechi Pietro?Emiliano?Doneddu Anna?Laura?Rassu Rita?Demurtas Anna?Scarabotto Pamela?Cassini Eloisa?Arbustini GianPietro?SechiEmail author 《BMC neurology》2015,15(1):256