全文获取类型
收费全文 | 97篇 |
免费 | 3篇 |
国内免费 | 4篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 6篇 |
2012年 | 2篇 |
2011年 | 1篇 |
2010年 | 2篇 |
2009年 | 2篇 |
2008年 | 3篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 2篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 3篇 |
排序方式: 共有104条查询结果,搜索用时 687 毫秒
81.
Hamish S. Sutherland Amy S.T. Tong Peter J. Choi Adrian Blaser Daniel Conole Scott G. Franzblau Manisha U. Lotlikar Christopher B. Cooper Anna M. Upton William A. Denny Brian D. Palmer 《Bioorganic & medicinal chemistry》2019,27(7):1292-1307
Bedaquiline is a new drug of the diarylquinoline class that has proven to be clinically effective against drug-resistant tuberculosis, but has a cardiac liability (prolongation of the QT interval) due to its potent inhibition of the cardiac potassium channel protein hERG. Bedaquiline is highly lipophilic and has an extremely long terminal half-life, so has the potential for more-than-desired accumulation in tissues during the relatively long treatment durations required to cure TB. The present work is part of a program that seeks to identify a diarylquinoline that is as potent as bedaquiline against Mycobacterium tuberculosis, with lower lipophilicity, higher clearance, and lower risk for QT prolongation. Previous work led to the identification of compounds with greatly-reduced lipophilicity compounds that retain good anti-tubercular activity in vitro and in mouse models of TB, but has not addressed the hERG blockade. We now present compounds where the C-unit naphthalene is replaced by a 3,5-dialkoxy-4-pyridyl, demonstrate more potent in vitro and in vivo anti-tubercular activity, with greatly attenuated hERG blockade. Two examples of this series are in preclinical development. 相似文献
82.
为探究非结核分枝杆菌(nontuberculous mycobacterium,NTM)肺病临床分离株的菌种分布及临床特征, 对2017年5月―2018年10月就诊于复旦大学附属中山医院的90例NTM肺病患者的样本进行分析。采用快速全自动分枝杆菌培养和药物敏感检测系统(BACTEC MGIT960 System)或改良罗氏培养法对90例患者的采集样本进行培养,利用基质辅助激光解析/电离飞行时间质谱(matrix assisted laser desorption/ionization time of flight mass spectrometry,MALDI-TOF MS)进行菌种鉴定,并对回顾性分析收集的90例患者的临床资料进行分析。结果NTM菌种鉴定为9种,其中慢速生长分枝杆菌65例,以胞内分枝杆菌(54.4%,49/90)占多数;快速生长分枝杆菌25例,以脓肿分枝杆菌(22.2%,20/90)占多数。90例患者中确诊67例、疑似23例。确诊患者中少见菌种所占比例较低(6.0% vs 26.1%,P = 0.016)。确诊与疑似患者在临床表现方面未见显著差异,但确诊患者有抗NTM治疗史的比例显著高于疑似患者(85.1% vs 4.3%,P < 0.001)。确诊患者中,快速生长NTM肺病患者既往抗结核治疗史的比例显著高于慢速生长组(52.9% vs 24.0%,P = 0.036)。本研究结果为NTM肺病的临床诊治提供了数据参考。 相似文献
83.
Roles of the three Mycobacterium smegmatis katG genes for peroxide detoxification and isoniazid susceptibility
下载免费PDF全文
![点击此处可从《Microbiology and immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
84.
85.
86.
The continuous emergence and rapid spread of a multidrug-resistant strain of bacterial pathogens have demanded the discovery and development of new antibacterial agents. A highly conserved prokaryotic cell division protein FtsZ is considered as a promising target by inhibiting bacterial cytokinesis. Inhibition of FtsZ assembly restrains the cell-division complex known as divisome, which results in filamentation, leading to lysis of the cell. This review focuses on details relating to the structure, function, and influence of FtsZ in bacterial cytokinesis. It also summarizes on the recent perspective of the known natural and synthetic inhibitors directly acting on FtsZ protein, with prominent antibacterial activities. A series of benzamides, trisubstituted benzimidazoles, isoquinolene, guanine nucleotides, zantrins, carbonylpyridine, 4 and 5-Substituted 1-phenyl naphthalenes, sulindac, vanillin analogues were studied here and recognized as FtsZ inhibitors that act either by disturbing FtsZ polymerization and/or GTPase activity. Doxorubicin, from a U.S. FDA, approved drug library displayed strong interaction with FtsZ. Several of the molecules discussed, include the prodrugs of benzamide based compound PC190723 (TXA-709 and TXA707). These molecules have exhibited the most prominent antibacterial activity against several strains of Staphylococcus aureus with minimal toxicity and good pharmacokinetics properties. The evidence of research reports and patent documentations on FtsZ protein has disclosed distinct support in the field of antibacterial drug discovery. The pressing need and interest shall facilitate the discovery of novel clinical molecules targeting FtsZ in the upcoming days. 相似文献
87.
Anti-cord factor (trehalose 6,6'dimycolate) IgG antibody in tuberculosis patients recognizes mycolic acid subclasses. 总被引:1,自引:0,他引:1
The detection of anti-cord factor (trehalose 6,6'-dimycolate) IgG antibody in active (smear-and/or culture-positive) and inactive (smear-and culture-negative) tuberculosis patients is a useful serodiagnostic tool that can be used for early clinical diagnosis of the disease. We estimated the titers of anticord factor IgG antibody in the sera of tuberculosis patients, and compared them with those of Mycobacterium avium-infected patients. Most of the serum samples obtained from the tuberculosis patients were highly reactive against M. tuberculosis (MTB) cord factor isolated from M. tuberculosis H37Rv, a human-type mycobacterial strain, whereas they were less reactive against M. avium (MAC) cord factor. Similarly, most of the serum samples of the MAC-infected patients were highly reactive against MAC cord factor and less reactive against MTB cord factor. These results suggest that anti-cord factor IgG antibody recognizes the mycolic acid subclasses as an epitope which comprises cord factor, since MTB and MAC cord factor differ in mycolic acid subclasses and molecular species composition. To clarify the exact antigenic epitope in cord factor and to find out a more sensitive and specific diagnostic test antigen, we examined the reactivity of patients' sera to glycolipids containing trehalose (cord factor and sulfolipid) obtained from various mycobacterial species. Furthermore, the reactivity of human antisera to various mycolic acid subclasses (alpha-, methoxy and keto mycolic acids) of MTB cord factor was compared. We found that anti-cord factor IgG antibody in the sera of human tuberculosis patients most strikingly recognized methoxy mycolic acid in the cord factor of M. tuberculosis, whereas it recognized alpha- and keto mycolic acids weakly. Pre-absorption studies of antibody with MTB cord factor or methoxy mycolic acid methyl ester showed that anti-cord factor antibody was absorbed partially, but consistently. This is the first report describing that the specific subclass of mycolic acid from mycobacteria is antigenic in the humoral immune system of human tuberculosis infection. 相似文献
88.
A competitive PCR method with standard DNA (MIMIC) was developed for the rapid detection and semiquantitation of Mycobacterium avium (M. avium) using primers specific for the alpha antigen sequence of the bacteria. DNA from both M. avium and Mycobacterium marinum was amplified by polymerase chain reaction (PCR), but only M. avium could be detected by subsequent blotting confirmation with a probe specific for the bacteria. With the PCR and subsequent dot blot hybridization, as little as 10 fg of the M. avium DNA could be detected, equivalent to about 2 cells of the mycobacteria. In addition, we could distinguish 10(5) CFUs of M. avium from 10(4) CFUs or less by competitive PCR using a MIMIC. The present competitive PCR test enabled rapid identification and semiquantitation of M. avium, and could be used clinically to monitor disease severity and response to treatment of human M. avium disease. 相似文献
89.
Iron uptake and intracellular metal transfer in mycobacteria mediated by xenosiderophores 总被引:1,自引:1,他引:0
Berthold F. Matzanke Rudolf Böhnke Ute Möllmann Rolf Reissbrodt Volker Schünemann Alfred X. Trautwein 《Biometals》1997,10(3):193-203
Growth promotion was tested using M. smegmatis wild type strain, an exochelin-deficient mutant, and M. fortuitum employing a broad variety of xenosiderophores including hydroxamates, catecholates and a-hydroxy carboxylic acids. The experiments revealed that utilization of siderophore-bound iron is substrate specific suggesting high-affinity siderophore receptor and transport systems. Concentration-dependent uptake of a selected xenosiderophore (fericrocin) in M. smegmatis showed saturation kinetics and uptake was inhibited by respiratory poisons. In situ Mössbauer spectroscopy of ferricrocin uptake in M. smegmatis indicated rapid intracellular reductive removal of the metal excluding intracellular ferricrocin accumulation. The ultimate intracellular iron pool is represented by a compound ( = 0.43 mm s, DE = 1.03 mm s) which has also been found in many other microorganisms and does not represent a bacterioferritin, cytochrome or iron-sulfur cluster. By contrast, iron uptake via citrate - a compound exhibiting a very low complex stability constant - involves ligand exchange with mycobactin. Mycobactin has merely a transient role. The ultimate storage compound is an E.coli-type bacterioferritin, in which over 90% of cellular iron is located. 相似文献
90.
Kyoko Enomoto Shiro Oka Nagatoshi Fujiwara Takashi Okamoto Yoshinari Okuda Ryoji Maekura Tetsuo Kuroki Ikuya Yano 《Microbiology and immunology》1998,42(10):689-696
Mycobacterium avium-intracellulare complex (MAC) is one of the most important opportunistic pathogens, particularly in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine whether an enzyme-linked immunosorbent assay (ELISA) using trehalose 6,6′-dimycolate (TDM) as an antigen can be used for the rapid serodiagnosis of MAC infection. We also identified MAC serotypes by ELISA using serotype-specific glycopeptidolipid (GPL) antigen. To confirm our findings, the thin-layer chromatographic (TLC) behavior of serotype-specific GPL of the strains isolated from MAC-infected patients was also tested. Forty patients infected with MAC and 30 healthy controls were tested. Thirty-two of the 40 MAC-infected patients had higher titers of serum antibodies against MAC TDM than against MTB TDM, while all 30 healthy control sera were unreactive to MAC TDM and MTB TDM. Results of the GPL ELISA indicated that 20 of the 40 MAC-infected patients' sera were reactive against serotype 4 GPL, 3 against serotype 8 GPL, and 1 against serotype 16 GPL. A TLC analysis of the GPL of the 40 MAC isolates showed that 16 strains were of serotype 4, 5 of serotype 8, and 2 of serotype 16. Results of the GPL ELISA were in good accord with those of the TLC analysis for most patients. Our findings suggest that ELISA using TDM is useful for rapid serodiagnosis of MAC infection, and that complementary ELISA testing using serotype-specific GPL gives additional detailed information concerning MAC serotypes. 相似文献