全文获取类型
收费全文 | 179篇 |
免费 | 4篇 |
专业分类
基础医学 | 17篇 |
临床医学 | 36篇 |
内科学 | 5篇 |
皮肤病学 | 3篇 |
神经病学 | 2篇 |
特种医学 | 1篇 |
外科学 | 8篇 |
综合类 | 19篇 |
预防医学 | 28篇 |
药学 | 60篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 2篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 11篇 |
2013年 | 10篇 |
2012年 | 14篇 |
2011年 | 11篇 |
2010年 | 10篇 |
2009年 | 14篇 |
2008年 | 10篇 |
2007年 | 16篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1985年 | 3篇 |
排序方式: 共有183条查询结果,搜索用时 15 毫秒
81.
目的 对多重耐药克雷伯菌属中喹诺酮类耐药相关基因的分布和变异情况进行分析.方法 连续收集2010年2月至2012年3月南京医科大学附属淮安第一医院住院患者中分离的多重耐药克雷伯菌共20株,用分子鉴定法鉴定菌种,再用聚合酶链反应(PCR)法分析喹诺酮类药物作用靶位基因gyrA与parC,以及可移动遗传元件介导的喹诺酮类耐药基因(qnrA、qnrB、qnrS、qepA、aac (6 ′)-Ⅰ b-cr).结果 本组20株克雷伯菌中,19株为肺炎克雷伯菌,1株为变栖克雷伯菌.20株克雷伯菌均检测到gyrA和parC基因,其中gyrA基因突变率为55.0% (11/20),parC基因突变率为55.0%(11/20);aac(6′)-Ⅰ b-cr基因阳性率为50.0%(10/20),qnrA基因阳性率为5.0%(1/20),qnrB基因阳性率为15.0%(3/20).其中6号株与10号株的gyrA与parC基因均为新的变异型(美国GenBank 登录号分别为:JX123016、JX123017与JX144393、JX144394).结论 肺炎克雷伯菌中gyrA和parC基因同时为新的变异型属国内首次报道,该菌对喹诺酮类药物的耐药主要与喹诺酮类耐药决定区突变相关. 相似文献
82.
《Joint, bone, spine : revue du rhumatisme》2014,81(6):485-492
Drug-induced tendon toxicity is rare but often underestimated. To date, four main drug classes have been incriminated in tendinopathies. Quinolones and long-term glucocorticoids are the most widely known, but statins and aromatase inhibitors can also induce tendon damage. The specific pathophysiological mechanisms responsible for drug-induced tendinopathies remain unknown. Proven risk factors have been identified, such as age older than 60 years, pre-existing tendinopathy, and potentiation of toxic effects when several drug classes are used in combination. Mean time to symptom onset varies from a few days with quinolones to several months with statins and several years for long-term glucocorticoid therapy. The most common sites of involvement are the lower limb tendons, most notably the body of the Achilles tendon. The first part of this review discusses tendon anatomy and the pathophysiology and radiological manifestations of tendinopathies. The second part provides details on the main characteristics of each of the drugs classes associated with tendon toxicity. 相似文献
83.
Lev Ostrer Rachel F. Khodursky James R. Johnson Hiroshi Hiasa Arkady Khodursky 《International journal of antimicrobial agents》2019,53(3):318-324
Fluoroquinolone (FQ)-resistant bacteria pose a major global health threat. Unanalysed genomic data from thousands of sequenced microbes likely contain important hints regarding the evolution of FQ resistance, yet this information lies fallow. Here we analysed the co-occurrence patterns of quinolone resistance mutations in genes encoding the FQ drug targets DNA gyrase (gyrase) and topoisomerase IV (topo-IV) from 36,402 bacterial genomes, representing 10 Gram-positive and 10 Gram-negative species. For 19 species, the likeliest routes toward resistance mutations in both targets were determined, and for 5 species those mutations necessary and sufficient to predict FQ resistance were also determined. Target mutation hierarchy was fixed in all examined Gram-negative species, with gyrase being the primary and topo-IV the secondary quinolone target, as well as in six of nine Gram-positive species, with topo-IV being the primary and gyrase the secondary target. By contrast, in three Gram-positive species (Staphylococcus haemolyticus, Streptococcus pneumoniae and Streptococcus suis), under some conditions gyrase became the primary and topo-IV the secondary target. The path through individual resistance mutations varied by species. Both linear and branched paths were identified in Gram-positive and Gram-negative organisms alike. Finally, FQ resistance could be predicted based solely on target gene quinolone resistance mutations for Acinetobacter baumannii, Escherichia coli and Staphylococcus aureus, but not Klebsiella pneumoniae or Pseudomonas aeruginosa. These findings have important implications both for sequence-based diagnostics and for understanding the emergence of FQ resistance. 相似文献
84.
85.
86.
Mechanism of quinolone resistance in Staphylococcus aureus 总被引:4,自引:0,他引:4
M. Tanaka T. Wang Y. Onodera Y. Uchida K. Sato 《Journal of infection and chemotherapy》2000,6(3):131-139
The resistance mechanisms to fluoroquinolones in Staphylococcus aureus were clarified by analyzing mutations in the genes encoding target enzymes, and examining the expression of the efflux pump,
and determining the inhibitory activities of fluoroquinolones against the altered enzymes. Mutations in the grlA and gyrA genes of 344 clinical strains of S. aureus isolated in 1994 in Japan were identified by combinations of methods – single-strand conformation polymorphism analysis,
restriction fragment length analysis, and direct sequencing – to identify possible relationships with fluoroquinolone resistance.
Five types of single-point mutations and four types of double mutations were observed in the grlA gene in 204 strains (59.3%). Four types of single-point mutations and four types of double mutations were found in the gyrA gene in 188 strains (54.7%). Among these mutations, the grlA mutation of TCC → TTC or TAC (Ser-80 → Phe or Tyr) and the gyrA mutation of TCA → TTA (Ser-84 → Leu) were the principal ones, being detected in 137 (39.8%) and 121 (35.2%) isolates, respectively.
A total of 15 types of mutation combinations within both genes were related to ciprofloxacin resistance (MIC ≧3.13 μg/ml)
and were present in 193 mutants (56.1%). Strains containing mutations in both genes were highly resistant to ciprofloxacin
(MIC50 =50 μg/ml). Those strains with the Ser-80 → Phe or Tyr alteration in grlA, but wild type in gyrA showed a lower level of ciprofloxacin resistance (MIC50≦12.5 μg/ml). Levofloxacin was active against 68 of 193 isolates (35.2%) with mutations at codon 80 of grlA in the presence or absence of concomitant mutations at codons 73, 84, or 88 in gyrA (MIC ≦6.25 μg/ml). Sitafloxacin (DU-6859a) showed good activity in 186 of 193 isolates (96.4%), with an MIC of ≦6.25 μg/ml.
The contribution of membrane-associated multidrug efflux protein (NorA) expression to fluoroquinolone resistance was clarified
by the checker-board titration method for determining the MIC of norfloxacin alone and in combination with carbonyl cyanide
m-chlorophenylhydrazone. Among 344 clinical isolates, 139 strains (40.4%), in which the MIC of norfloxacin varied from 1.56
to >800 μg/ml, overexpressed the NorA protein. GrlA and GrlB proteins of topoisomerase IV, and GyrA and GyrB proteins of DNA
gyrase encoded by genes with or without mutations were purified separately. The inhibitory activities of fluoroquinolones
against the topoisomerase IV which contained a single amino acid change (Ser → Phe at codon 80, Glu → Lys at codon 84 of grlA, and Asp → Asn at codon 432 of grlB) were from 5 to 95 times weaker than the inhibitory activities against the non-altered enzyme. These results suggest that
the mutations in the corresponding genes may confer quinolone resistance; the active efflux pump, NorA, was considered to
be the third quinolone-resistance mechanism. The numerous and complicated mutations seen may explain the rapid and widespread
development of quinolone resistance described in S. aureus. Sitafloxacin showed good antibacterial activity against ciprofloxacin- or levofloxacin-resistant mutants because of its
high inhibitory activity against both topoisomerase IV and DNA gyrase.
Received: March 3, 2000 / Accepted: May 2, 2000 相似文献
87.
88.
《Journal of infection and chemotherapy》2020,26(11):1139-1145
BackgroundPlasmid-encoded quinolone resistance protein Qnr is an important factor in bacterial resistance to quinolones. Qnr interacts with DNA gyrase and reduces susceptibility to quinolones. The gene qnr likely spreads rapidly among Enterobacteriaceae via horizontal gene transfer. Though the vast amounts of epidemiological data are available, molecular details of the contribution of QnrB19, the predominant Qnr in Salmonella spp., to the acquisition of quinolone resistance has not yet been understood well.ObjectiveWe aimed to examine the role of QnrB19 in quinolone resistance acquisition using recombinant Salmonella Typhimurium DNA gyrases and QnrB19.Materials and methodsRecombinant QnrB19 was expressed in E. coli and purified by Ni-NTA agarose column chromatography. DNA supercoiling activities of recombinant Salmonella Typhimurium DNA gyrase were assessed with or without QnrB19 under the existence of three quinolones to measure IC50s, the concentration of each quinolone required for 50% inhibition in vitro.ResultsThe IC50s of norfloxacin, ciprofloxacin and nalidixic acid against DNA gyrases were measured to be 0.30, 0.16 and 17.7 μg/mL, respectively. The addition of QnrB19 increased the IC50s of norfloxacin and ciprofloxacin to be 0.81 and 0.48 μg/mL, respectively, where no effect of QnrB19 was observed on the IC50 of nalidixic acid.ConclusionQnrB19 was shown for the first time in vitro to have ability to grant non-classical quinolone resistance to S. Typhimurium DNA gyrase. Structural insight on quinolones in this study may contribute to investigate drugs useful for preventing the spread of plasmid carrying PMQR along with other factors associating with antimicrobial resistance in S. Typhimurium and other bacteria. 相似文献
89.
90.
多药耐药肺炎克雷伯菌喹诺酮类耐药相关基因研究 总被引:8,自引:7,他引:1
目的 了解多药耐药肺炎克雷伯菌(MDRKP)喹诺酮类耐药机制.方法 对一组25株MDRKP进行了染色体介导和质粒介导的耐药相关基因进行检测和分析.结果 25株中,有19种存在gyrA基因突变(76.0%);9株存在aac(6′)-Ⅰ b-Cr(36.0%);2株存在qnrA1基因(8.0%)、2株存在qnrB基因(qnrB4-like)(8.0%)、3株存在qnrS1基因(12.0%);25株均存在mdfA基因,未检出qepA基因.结论 在MDRKP中,gyrA基因突变是喹诺酮类耐药的主要原因. 相似文献