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81.
82.
Burugina Nagaraja S Satyanarayana S Chadha SS Kalemane S Jaju J Achanta S Reddy K Potharaju V Shamrao SR Dewan P Rony Z Tetali S Anchala R Kannuri NK Harries AD Singh SK 《PloS one》2011,6(10):e25698
Setting
Seven districts in Andhra Pradesh, South IndiaObjectives
To a) determine treatment outcomes of patients who fail first line anti-TB treatment and are not placed on an multi-drug resistant TB (MDR-TB) regimen, and b) relate the treatment outcomes to culture and drug susceptibility patterns (C&DST).Design
Retrospective cohort study using routine programme data and Mycobacterium TB Culture C&DST between July 2008 and December 2009.Results
There were 202 individuals given a re-treatment regimen and included in the study. Overall treatment outcomes were: 68 (34%) with treatment success, 84 (42%) failed, 36 (18%) died, 13 (6.5%) defaulted and 1 transferred out. Treatment success for category I and II failures was low at 37%. In those with positive cultures, 81 had pan-sensitive strains with 31 (38%) showing treatment success, while 61 had drug-resistance strains with 9 (15%) showing treatment success. In 58 patients with negative cultures, 28 (48%) showed treatment success.Conclusion
Treatment outcomes of patients who fail a first-line anti-TB treatment and who are not placed on an MDR-TB regimen are unacceptably poor. The worst outcomes are seen among category II failures and those with negative cultures or drug-resistance. There are important programmatic implications which need to be addressed. 相似文献83.
William Kemnitzer Nilantha Sirisoma Bao Nguyen Songchun Jiang Shailaja Kasibhatla Candace Crogan-Grundy Ben Tseng John Drewe Sui Xiong Cai 《Bioorganic & medicinal chemistry letters》2009,19(11):3045-3049
N-(2-Methylphenyl)-9-oxo-9H-fluorene-1-carboxamide (2a) was identified as a novel apoptosis inducer through our caspase- and cell-based high-throughput screening assay. Compound 2a was found to be active with sub-micromolar potencies for both caspase induction and growth inhibition in T47D human breast cancer, HCT116 human colon cancer, and SNU398 hepatocellular carcinoma cancer cells. It arrested HCT116 cells in G2/M followed by apoptosis as assayed by the flow cytometry. Structure–activity relationship (SAR) studies of the carboxamide group identified the lead compound N-(2-(1H-pyrazol-1-yl)phenyl)-9-oxo-9H-fluorene-1-carboxamide (6s). Compound 6s, with increased aqueous solubility, was found to retain the broad activity in the caspase activation assay and in the cell growth inhibition assay with sub-micromolar EC50 and GI50 values in T47D, HCT116, and SNU398 cells, respectively. 相似文献
84.
Sulindac is an FDA-approved non-steroidal anti-inflammatory drug with documented anticancer activities. Our recent studies showed that sulindac selectively enhanced the killing of cancer cells exposed to oxidizing agents via production of reactive oxygen species (ROS) resulting in mitochondrial dysfunction. This effect of sulindac and oxidative stress on cancer cells could be related to the defect in respiration in cancer cells, first described by Warburg 50 years ago, known as the Warburg effect. We postulated that sulindac might enhance the selective killing of cancer cells when combined with any compound that alters mitochondrial respiration. To test this hypothesis we have used dichloroacetate (DCA), which is known to shift pyruvate metabolism away from lactic acid formation to respiration. One might expect that DCA, since it stimulates aerobic metabolism, could stress mitochondrial respiration in cancer cells, which would result in enhanced killing in the presence of sulindac. In this study, we have shown that the combination of sulindac and DCA enhances the selective killing of A549 and SCC25 cancer cells under the conditions used. As predicted, the mechanism of killing involves ROS production, mitochondrial dysfunction, JNK signaling and death by apoptosis. Our results suggest that the sulindac-DCA drug combination may provide an effective cancer therapy. 相似文献
85.
Zhang HZ Drewe J Tseng B Kasibhatla S Cai SX 《Bioorganic & medicinal chemistry》2004,12(13):3649-3655
A series of indole-2-carboxylic acid benzylidene-hydrazides has been identified as a new class of potent apoptosis inducers through a novel cell-based caspase HTS assay. The screening hit, 5-chloro-3-methyl-indole-2-carboxylic acid (4-nitrobenzylidene)-hydrazide (3a), was found to arrest T47D cells in G(2)/M and to induce apoptosis as measured by the flow cytometric analysis assay. A SAR study was carried out by modification of the substitutions on the indole and benzene rings. Substitution at the 3-position of the indole ring was found to be important for apoptotic activity. A 20-fold increase of apoptotic activity was achieved from screening hit 3a to 5-methyl-3-phenyl-indole-2-carboxylic acid (4-methylbenzylidene)-hydrazide (9a) and 5-chloro-3-phenyl-indole-2-carboxylic acid (4-nitrobenzylidene)-hydrazide (9b), with EC(50) value of 0.1microM in the caspase activation assay in T47D breast cancer cells. Compound 9b also was found to be highly active in a standard growth inhibition assay with a GI(50) value of 0.9microM in T47D cells. Compound 3a and its analogs were found to inhibit tubulin polymerization, which is the most probable primary mechanism of action of these compounds. 相似文献
86.
The expression and regulation of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5, was studied in intestinal cells. Both PDE5A1 and PDE5A2 splice forms were cloned from the cDNA prepared from human colonic T84 cells, and PDE5 activity was dependent on increases in intracellular cGMP levels which correlated with increased phosphorylation of the enzyme. PDE5 expression was monitored in different regions of the gastrointestinal tract and nearly 50% of the phosphodiesterase activity in the duodenum, jejunum, ileum and colon was inhibited by sildenafil citrate. Administration of the stable toxin to intestinal loops resulted in activation of PDE5. Inhibition of PDE5 by sildenafil citrate led to fluid accumulation in loops, suggesting a possible explanation for the side effect of diarrhoea observed in individuals administered sildenafil citrate. Our results therefore represent the first study on the expression and regulation of PDE5 in intestinal tissue, and indicate that mechanisms to control its activity may have important consequences in intestinal physiology. 相似文献
87.
A heterologous gene probe encoding the α and β subunits of the Pseudomonas cepacia protocatechuate 3,4-dioxygenase (PCD) was used to detect its homolog in the genome of Bradyrhizobium japonicum USDA110. Three cosmid clones carrying a 2.2-kb BamHI insert showed high levels of PCD activity. SacI digestion of one of the genomic clones, pBjG17, produced a 2.5-kb insert DNA that complemented a PCD mutant of P. cepacia. 相似文献
88.
An endogenous inhibitor of calcium activated neutral proteinase has been purified from human placenta. The procedure included
chromatography on DEAE cellulose, Ultrogel AcA 22 and milli calcium activated neutral proteinase-sepharose in succession.
Endogenous calcium activated neutral proteinase inhibitor was a tetramer with identical subunits of molecular weight 68 kDa.
It was specific for milli calcium activated neutral proteinase (Calpain II) which is inhibited by the formation of an inactive
enzyme-inhibitor complex and not by sequestering Ca2+ from the medium. Although micro calcium activated neutral proteinase (Calpain I) was not inhibited by endogenous calcium
activated neutral proteinase inhibitor, it was protected from autolysis in the presence of the inhibitor. The placental endogenous
calcium activated neutral proteinase inhibitor thus regulates Ca2+ activated proteolysis by ensuring micro calcium activated neutral proteinase activity, while inhibiting milli calcium activated
neutral proteinase. 相似文献
89.
Venkata Mohan S Rama Krishna M Muralikrishna P Shailaja S Sarma PN 《Bioresource technology》2007,98(15):2905-2910
Substrate leaching experiments were performed to study the relative leaching potential of pendimethalin in various types of soil matrices. Pendimethalin leaching showed up to a depth of 30 cm in all the studied soil matrices, irrespective of pH conditions used. The leaching potential of pendimethalin was assessed at various pH conditions. Comparatively higher leaching potential was observed in basic conditions compared to the neutral and acid conditions of soil. Soil phase bioremediation of pendimethalin was also performed on all the soil matrices. Among the studied variations, bioremediation experiments performed in presence of sunlight showed higher efficiency. Bioaugmentation along with sunlight showed higher remediation efficiency in all the studied soil matrices. Biostimulation did not respond positively on the progress of bioremediation. 相似文献
90.
Seung-Hwan Lee Ira Gantz Elizabeth Round Melanie Latham Edward A. O’Neill Paulette Ceesay Shailaja Suryawanshi Keith D. Kaufman Samuel S. Engel Eseng Lai 《BMC endocrine disorders》2017,17(1):70