全文获取类型
收费全文 | 432篇 |
免费 | 88篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 25篇 |
妇产科学 | 3篇 |
基础医学 | 112篇 |
口腔科学 | 11篇 |
临床医学 | 57篇 |
内科学 | 90篇 |
皮肤病学 | 17篇 |
神经病学 | 26篇 |
特种医学 | 22篇 |
外国民族医学 | 1篇 |
外科学 | 32篇 |
综合类 | 28篇 |
预防医学 | 53篇 |
眼科学 | 8篇 |
药学 | 15篇 |
肿瘤学 | 13篇 |
出版年
2018年 | 8篇 |
2017年 | 14篇 |
2016年 | 6篇 |
2015年 | 8篇 |
2014年 | 7篇 |
2013年 | 14篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 9篇 |
2009年 | 13篇 |
2008年 | 16篇 |
2007年 | 15篇 |
2006年 | 15篇 |
2005年 | 14篇 |
2004年 | 26篇 |
2003年 | 17篇 |
2002年 | 15篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1997年 | 3篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 13篇 |
1990年 | 6篇 |
1989年 | 16篇 |
1988年 | 7篇 |
1987年 | 12篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 8篇 |
1980年 | 3篇 |
1979年 | 11篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 11篇 |
1974年 | 18篇 |
1973年 | 10篇 |
1972年 | 11篇 |
1971年 | 6篇 |
1970年 | 6篇 |
1967年 | 5篇 |
1965年 | 3篇 |
1963年 | 3篇 |
排序方式: 共有520条查询结果,搜索用时 156 毫秒
11.
12.
Intracellular methicillin selection of Listeria monocytogenes mutants unable to replicate in a macrophage cell line. 总被引:13,自引:1,他引:13
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A Camilli C R Paynton D A Portnoy 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(14):5522-5526
To dissect the determinants of Listeria monocytogenes that are required for pathogenicity, we designed an intracellular selection protocol based on penicillin selection to isolate mutants defective for intracellular growth. Eight independent mutants obtained by insertion of Tn916 were isolated that were resistant to methicillin treatment following internalization by the J774 macrophage-like cell line. Seven mutants were absolutely defective for intracellular growth, whereas one showed abortive intracellular growth. The majority of the mutants were nonhemolytic and lacked a secreted 58-kDa polypeptide thought to be the L. monocytogenes hemolysin, listeriolysin O. Southern blot analysis indicated that one mutant contained a Tn916 insertion in hlyA, the listeriolysin O structural gene, which resulted in a truncated listeriolysin O polypeptide, whereas another mutant contained an insertion immediately upstream of hlyA, which resulted in reduced expression of listeriolysin O. The other mutants contained Tn916 insertions in genes other than hlyA, although all but one were nonhemolytic. Revertants isolated by their ability to grow within tissue culture cells regained hemolytic activity. These data show that intracellular methicillin selection facilitates isolation of mutations in genes required for intracellular growth and strengthens the premise that listeriolysin O is essential for intracellular growth. 相似文献
13.
14.
Alexander A. Firsov Maria V. Golikova Elena N. Strukova Yury A. Portnoy Andrey V. Romanov Mikhail V. Edelstein Stephen H. Zinner 《Antimicrobial agents and chemotherapy》2015,59(2):1014-1019
Bacterial resistance studies using in vitro dynamic models are highly dependent on the starting inoculum that might or might not contain spontaneously resistant mutants (RMs). To delineate concentration-resistance relationships with linezolid-exposed Staphylococcus aureus, a mixed inoculum containing both susceptible cells and RMs was used. An RM selected after the 9th passage of the parent strain (MIC, 2 μg/ml) on antibiotic-containing media (RM9; MIC, 8 μg/ml) was chosen for the pharmacodynamic studies, because the mutant prevention concentration (MPC) of linezolid against the parent strain in the presence of RM9 at 102 (but not at 104) CFU/ml did not differ from the MPC value determined in the absence of the RMs. Five-day treatments with twice-daily linezolid doses were simulated at concentrations either between the MIC and MPC or above the MPC. S. aureus RMs (resistant to 2× and 4× MIC but not 8× and 16× MIC) were enriched at ratios of the 24-h area under the concentration-time curve (AUC24) to the MIC that provide linezolid concentrations between the MIC and MPC for 100% (AUC24/MIC, 60 h) and 86% (AUC24/MIC, 120 h) of the dosing interval. No such enrichment occurred when linezolid concentrations were above the MIC and below the MPC for a shorter time (37% of the dosing interval; AUC24/MIC, 240 h) or when concentrations were consistently above the MPC (AUC24/MIC, 480 h). These findings obtained using linezolid-susceptible staphylococci supplemented with RMs support the mutant selection window hypothesis. This method provides an option to delineate antibiotic concentration-resistance relationships with bacteria that exhibit low mutation frequencies. 相似文献
15.
Regional or localized pericarditis has been infrequently reported. We report a patient with systemic lupus erythematosus (SLE), who presented with retrosternal pleuritic-type chest pain without audible friction rub, electrocardiographic changes or detectable pericardial effusion on echocardiography. Computed tomography, however, revealed a circumscribed area of pericardial inflammation, suggesting a diagnosis of localized lupus-associated pericarditis. This case demonstrates that localized pericarditis may occur in SLE and that chest CT may be required as part of the work-up in the diagnosis of lupus pericarditis. 相似文献
16.
Kamar M Portnoy O Bar-Dayan A Amitai M Munz Y Ayalon A Zmora O 《Diseases of the colon and rectum》2004,47(7):1242-1246
Computed tomography colonography, also termed virtual colonoscopy, is a new imaging method to investigate the colon, which may be a potential alternative to the conventional endoscopic colonoscopy in some cases. The high safety profile of this imaging method was considered as an additional advantage of this procedure. A case of colonic perforation in computed tomography colonography is presented, highlighting a potential risk related to this procedure. It is assumed that perforation was the result of overinflation of air into an obstructed colon caused by a lesion at the rectosigmoid junction. Thus, it is suggested that in such cases, air insufflation should be gradual, thereby minimizing the risk of perforation. 相似文献
17.
18.
SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis 总被引:12,自引:0,他引:12
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lenz LL Mohammadi S Geissler A Portnoy DA 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(21):12432-12437
Pathogenic bacteria secrete proteins that promote invasion of host tissues and resistance to immune responses. However, secretion mechanisms that contribute to the enormous morbidity and mortality of Gram-positive bacteria are largely undefined. An auxiliary protein secretion system (SecA2) has recently emerged in Listeria monocytogenes and eight other Gram-positive pathogens. Here, a proteomics approach identified seventeen SecA2-dependent secreted and surface proteins of L. monocytogenes, the two most abundant of which [the p60 and N-acetylmuramidase (NamA) autolysins] hydrolyze bacterial peptidoglycan (PGN) and contribute to host colonization. SecA2-deficient (DeltaSecA2) bacteria were rapidly cleared after systemic infection of murine hosts, and in cultured cells showed reduced cell-cell spread. p60 or NamA deficiencies (Deltap60 and DeltaNamA) caused intermediate reductions in bacterial virulence in vivo, yet showed no defect for infection of cultured cells. Restoration of virulence in Deltap60 bacteria required full-length p60 with an intact catalytic domain, suggesting that PGN hydrolysis by p60 is crucial for L. monocytogenes virulence. Coordinated PGN hydrolysis by p60 and NamA activities is predicted to generate a muramyl glycopeptide, glucosaminylmuramyl dipeptide (GMDP), which is known to modify host inflammatory responses. Thus, SecA2-dependent secretion may promote release of muramyl peptides that subvert host pattern recognition. 相似文献
19.
20.