全文获取类型
收费全文 | 152篇 |
免费 | 16篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 5篇 |
基础医学 | 28篇 |
口腔科学 | 3篇 |
临床医学 | 12篇 |
内科学 | 26篇 |
皮肤病学 | 3篇 |
神经病学 | 5篇 |
外科学 | 21篇 |
综合类 | 4篇 |
预防医学 | 9篇 |
眼科学 | 4篇 |
药学 | 26篇 |
中国医学 | 1篇 |
肿瘤学 | 10篇 |
出版年
2024年 | 1篇 |
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 11篇 |
2011年 | 7篇 |
2010年 | 5篇 |
2009年 | 6篇 |
2008年 | 3篇 |
2007年 | 4篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 4篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有169条查询结果,搜索用时 15 毫秒
41.
Powley MW Jayaraj K Gold A Ball LM Swenberg JA 《Chemical research in toxicology》2003,16(11):1448-1454
1,3-Butadiene (BD) is a rodent and human carcinogen. While several epoxides formed during BD metabolism are mutagenic and may contribute to BD carcinogenicity, another proposed metabolite, hydroxymethylvinyl ketone (HMVK), could also be involved. A significant quantity of HMVK is likely to be formed since it is a proposed intermediate in the metabolism of 3-butene-1,2-diol (BD-diol) to 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, the major mercapturic acid metabolite of BD in humans. In addition, BD-diol is a major BD metabolite in liver perfusion experiments in rodents. By analogy with other alpha,beta-unsaturated carbonyls, HMVK is likely to be mutagenic via formation of promutagenic 1,N(2)-propanodeoxyguanosine adducts. The objective of the current study was to investigate the formation of such adducts in vitro. The reaction between HMVK and dGuo yielded two major products shown to be identical by positive ion electrospray-MS, having protonated molecular ions with m/z consistent with HMVK-derived 1,N(2)-propanodeoxyguanosine (HMVK-dGuo). Rechromatography of each fraction yielded two fractions with retention times identical to those initially isolated, suggesting equilibration between two diastereomers. Two partially resolved sets of (1)H NMR signals were consistent with a 1:1 mixture of diastereomeric C-6-substituted adducts equilibrating slowly on an NMR time-scale. Following deglycosylation, C-6 substitution was verified by two-dimensional correlation NMR spectroscopy, indicating that the initial adducts were formed by Michael addition of dGuo-N1 to the terminal vinyl carbon followed by cyclization to the 1,N(2)-propano structure. Reactions with calf thymus DNA under physiological conditions yielded two sets of products. The first set had HPLC retention times and mass spectra identical to those of the previously characterized C-6-substituted HMVK-dGuo diastereomers. The second set had a molecular ion and fragmentation pattern identical to the C-6-substituted adducts and on this basis were assigned as the diastereomeric C-8 adducts. In addition to detecting HMVK-dGuo in treated DNA, the adducts were also present in control DNA. Overall, our research demonstrates that HMVK can form promutagenic DNA adducts and it therefore has the potential to play a role in BD-associated mutagenicity. 相似文献
42.
43.
44.
45.
G T Budd A Jayaraj D Grabowski D Adelstein L Bauer J Boyett R Bukowski S Murthy J Weick 《Cancer research》1990,50(22):7206-7211
We have performed two Phase I trials of the combination of dipyridamole, 5-fluorouracil (5-FU), and folinic acid in patients with advanced refractory malignancy, based upon in vitro evidence that dipyridamole can modulate the cytotoxicity of 5-FU. In the first trial, patients were treated every 4 wk with dipyridamole (50 mg/m2) p.o. every 6 h on Days 0 to 6, beginning 24 h prior to the i.v. administration of folinic acid (200 mg/m2) and escalating doses of i.v. 5-FU on Days 1 to 5. The maximum tolerated daily dose of 5-FU that could be given with this combination was 375 mg/m2. Because dipyridamole is extensively bound to plasma proteins, it was hypothesized that the concentrations of free dipyridamole achieved with a dose of 50 mg/m2 were inadequate to modulate the cytotoxicity of 5-FU and folinic acid. Therefore, a second Phase I trial of escalating dose of p.o. dipyridamole was performed. Folinic acid (200 mg/m2) and 5-FU (375 mg/m2) were given i.v. on Days 1 to 5 every 4 wk, beginning 24 h after the start of therapy with dipyridamole; dipyridamole was administered p.o. on Days 0 to 6 at doses of 75, 100, 125, 150, 175, or 200 mg/m2/dose to successive cohorts of patients. Dose-limiting neutropenia, mucositis, and nausea were produced at a dose of 200 mg/m2/dose; the recommended dose of dipyridamole for use in Phase II studies is 175 mg/m2 p.o. every 6 h, or 700 mg/m2/day. At this dose, a mean peak plasma concentration of total dipyridamole of 16.32 mumol and a mean peak plasma concentration of free dipyridamole of 38.30 nmol were observed. Trough concentrations of free dipyridamole averaged 60% of the peak concentrations. Objective antitumor responses were seen in a number of tumor types; five of 13 patients with breast cancer treated with high-dose p.o. dipyridamole, 5-FU, and folinic acid responded. High-dose p.o. dipyridamole can produce plasma concentrations of free dipyridamole within the range shown to modulate the cytotoxicity of 5-FU and other agents. Phase II trials of this combination are justified. 相似文献
46.
Rats pre-fed on a South Indian diet show a much higher incidence of ulceration of the stomach after pyloric ligation than those on a North Indian diet. Removing vegetables and pulses from the North Indian diet deprives it of its protective effect. Staple foodstuffs with a high buffer content (unmilled rice, unrefined wheat and a millet [ragi]) placed in the stomach after pyloric ligation are also protective, but those with a low buffer content (milled rice, tapioca, sorghum and maize) are not protective. Refined wheat, however, gives protection despite its low buffer content. The significance of these findings in relationship to the distribution of duodenal ulcer in India and Africa is discussed. 相似文献
47.
48.
Rachna Dave Prithi Jayaraj Puthuparampil K. Ajikumar Hiren Joshi Tom Mathews Vayalam P. Venugopalan 《Journal of biomaterials science. Polymer edition》2013,24(11):1305-1319
The study was aimed at assessing the potential of enzyme-embedded antibiotic-releasing polycaprolactone (PCL)-based electrospun fibres for tunable drug delivery. This was attempted by incorporation of gentamicin sulphate (GS) in the biocompatible polymer (PCL) matrix, with the degradation of the matrix being ensured by co-impregnating a polymer-degrading enzyme (lipase). Single phase solutions were obtained by hydrophobic ion pairing of GS and surfactant coating of lipase with an anionic surfactant, docusate sodium salt Aerosol OT (AOT). By electrospinning the solution, we could produce PCL fibres containing 11% (w/w) GS–AOT and 28?U (w/w) lipase–AOT. However, sustained release of GS was not obtained. FESEM analysis showed that the fibres did not undergo the expected degradation. Subsequent experiments with unmodified lipase gave satisfactory results; the polymer underwent degradation displaying characteristic perforations in the fibres, suggestive of ‘endo-attack’. By modulating the concentrations of lipase (1 to 28?U, w/w), we could obtain GS release rates that varied from 0.53 to 32?mg/ml/d. Accordingly, the lifetime of the fibres could be tuned (10?h to 25?days). The fibres showed excellent antibacterial activity against Staphylococcus aureus throughout their lifetime. 相似文献
49.
50.
Alison L Fisher Elizabeth DePuy Andrew Jayaraj Conrad Raab Matt Braun Michel Ellis-Hutchings Jin Zhang John D Rogers Donald G Musson 《Journal of pharmaceutical and biomedical analysis》2002,27(1-2):57-71
In vitro and in animals, I is a potent and specific peptidomimetic for the potential treatment of airway inflammation in the pathogenesis of asthma. Preclinical studies indicated extensive conversion of I to an active metabolite II, and thus, a very sensitive assay for I and II was needed to support an inhalation ascending-dose study in man. The LC/MS/MS plasma/urine assay method (1.0 ml of sample) involves the following: liquid-liquid extraction of acidified plasma into pentane-ethyl acetate (90:10 v/v); evaporation of the organic extract, reconstitution into methanol; addition of water to the methanolic extract and freezing. After thawing, the extract is centrifuged and the clear supernatant injected for chromatography. Extract is chromatographed on a YMC ODS-AM column (50 x 2.0 mm). For detection, a Sciex 365 LC/MS/MS with an electrospray inlet and used in the positive ion, multiple reaction monitoring mode was used to monitor precursor-->fragment ions of m/z 709-->594 for I and m/z 513-->380 for II. The plasma assay was linear over the concentration range of 0.1-100 ng/ml in plasma for I and II. Accuracy and precision for I ranged from 97.9 to 102.1% of nominal with a 0.84-10.65% CV; similarly for II, 98.0-101.7% and 1.39-9.28% CV, respectively. Extraction recovery averaged 63.7% for I and 64.9% for II. This general assay methodology may be applied to assay small acidic peptides and peptidomimetics from biological fluids by LC/MS/MS. 相似文献