全文获取类型
收费全文 | 835篇 |
免费 | 76篇 |
国内免费 | 1篇 |
出版年
2024年 | 5篇 |
2023年 | 5篇 |
2022年 | 14篇 |
2021年 | 27篇 |
2020年 | 19篇 |
2019年 | 20篇 |
2018年 | 23篇 |
2017年 | 24篇 |
2016年 | 30篇 |
2015年 | 42篇 |
2014年 | 42篇 |
2013年 | 32篇 |
2012年 | 44篇 |
2011年 | 38篇 |
2010年 | 20篇 |
2009年 | 23篇 |
2008年 | 22篇 |
2007年 | 25篇 |
2006年 | 24篇 |
2005年 | 27篇 |
2004年 | 13篇 |
2003年 | 19篇 |
2002年 | 22篇 |
2001年 | 23篇 |
2000年 | 20篇 |
1999年 | 28篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1992年 | 20篇 |
1991年 | 14篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 12篇 |
1987年 | 14篇 |
1986年 | 16篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1981年 | 4篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 8篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1969年 | 6篇 |
1936年 | 3篇 |
1928年 | 3篇 |
排序方式: 共有912条查询结果,搜索用时 31 毫秒
1.
(+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program. 相似文献
2.
The potent rat-liver mitogen 4-acetylaminofluorene (4AAF) is shown here to provide an effective replacement for the surgical procedure of 2/3 partial hepatectomy (2/3PH) in the in vivo rat-liver micronucleus assay described by Tates and his colleagues. This protocol modification enables the assay to be conducted on a routine basis. Control observations for both 2/3PH and 4AAF-treated rats are presented, together with evidence indicating 4AAF itself to be without activity in the assay, irrespective of the mitogenic stimulus. The activities of the rat carcinogens DMN, 2AAF, DMH and 6BT, and of the non-carcinogens 4AAF and 4N are demonstrated. Recommendations for the conduct of the modified assay are made. 相似文献
3.
M Ashby 《BMJ (Clinical research ed.)》1987,294(6588):1688-1689
4.
5.
Outer membrane protein mediating iron uptake via pyoverdinpss, the fluorescent siderophore produced by Pseudomonas syringae pv. syringae. 总被引:5,自引:5,他引:0
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In an iron-limited environment Pseudomonas syringae pv. syringae B301D produces a yellow-green fluorescent siderophore called pyoverdinpss which functions in high-affinity iron transport. Two-dimensional electrophoretic comparisons of the outer membrane proteins of strain B301D identified nine proteins which were expressed at low (50 nM) but not at high (10 microM) iron concentrations. Except for the minor protein 8e, the iron-regulated proteins exhibited high molecular weights ranging from approximately 74,000 to 80,000. A mutant of strain B301D incapable of iron uptake (Iu-) from ferric pyoverdinpss lacked the 74,000-molecular-weight protein 4a, which was the major iron-regulated outer membrane protein. In contrast, a nonfluorescent mutant (Flu-) unable to synthesize pyoverdinpss showed no quantitative or qualitative difference in its outer membrane profile from that of the wild-type strain. In plant pathogenicity tests the Iu- and Flu- strains caused typical brown necrotic and sunken lesions in immature sweet cherry fruit which were indistinguishable from those of the wild-type strain. Thus, excretion of pyoverdinpss and subsequent Fe(III) uptake do not have a determinative role in the pathogenicity or virulence of P. syringae pv. syringae. 相似文献
6.
D Scott S M Galloway R R Marshall M Ishidate D Brusick J Ashby B C Myhr 《Mutation research》1991,257(2):147-205
7.
Groups of male Alderley Park rats were dosed concomitantly with 2-acetylaminofluorene (2AAF) by gavage at doses between 0.01 mg/kg and 40 mg/kg, and livers sampled 2-72 h later. The liver of one group of animals was perfused to yield hepatocytes which were assayed in vitro for unscheduled DNA synthesis (UDS) via incorporation of tritiated thymidine and autoradiography. DNA was extracted from the livers of the other group and DNA adduct levels determined using the 32P-postlabelling technique. The major C-8 2-aminofluorene/guanosine adduct and 3 minor adducts were quantitated, enabling the relative sensitivity of the 2 techniques to be compared. A dose- and time-related UDS response was observed, which, at the most sensitive time-point (12 h) enabled DNA repair to be discerned at a dose level of 0.1-1 mg/kg of 2AAF, a response classified as formally positive at 5 mg/kg 2AAF. Only the C-8 adduct, as determined by 32P-postlabelling, was discernible at 0.01 mg/kg of 2AAF, although other adducts were visible on autoradiograms at higher dose levels. It is concluded that as part of a well-defined dose response, UDS can be discerned with confidence for doses of 2AAF between approximately 0.1 and 5 mg/kg, and DNA adducts for doses of 2AAF between approximately 0.01 and 1 mg/kg. Discernible UDS for 2AAF in the rat liver is apparent at approximately 13 DNA (total) adducts/10(8) nucleotides, or approximately 8 DNA (C-8) adducts/10(8) nucleotides. The presumed C-8 2-acetylaminofluorene/guanosine adduct, prepared by reaction of 2-acetoxy-2-acetylaminofluorene (2AAAF) with DNA, was a significant but unreliable marker of 2AAF/DNA adducts in the rat liver in vivo. DNA repair did not appear to remove DNA adducts selectively, and adducts remained in DNA when discernible DNA repair had ceased. 相似文献
8.
An analysis is presented in which are evaluated correlations among chemical structure, mutagenicity to Salmonella, and carcinogenicity to rats and mice among 301 chemicals tested by the U.S. NTP. Overall, there was a high correlation between structural alerts to DNA reactivity and mutagenicity, but the correlation of either property with carcinogenicity was low. If rodent carcinogenicity is regarded as a singular property of chemicals, then neither structural alerts nor mutagenicity to Salmonella are effective in its prediction. Given this, the database was fragmented and new correlations sought between the derived sub-groups. First, the 301 chemicals were segregated into six broad chemical groupings. Second, the rodent cancer data were partially segregated by target tissue. Using the previously assigned structural alerts to DNA reactivity (electrophilicity), the chemicals were split into 154 alerting chemicals and 147 non-alerting chemicals. The alerting chemicals were split into three chemical groups; aromatic amino/nitro-types, alkylating agents and miscellaneous structurally-alerting groups. The non-alerting chemicals were subjectively split into three broad categories; non-alerting, non-alerting containing a non-reactive halogen group, and non-alerting chemical with minor concerns about a possible structural alert. The tumor data for all 301 chemicals are re-presented according to these six chemical groupings. The most significant findings to emerge from comparisons among these six groups of chemicals were as follows: (a) Most of the rodent carcinogens, including most of the 2-species and/or multiple site carcinogens, were among the structurally alerting chemicals. (b) Most of the structurally alerting chemicals were mutagenic; 84% of the carcinogens and 66% of the non-carcinogens. 100% of the 33 aromatic amino/nitro-type 2-species carcinogens were mutagenic. Thus, for structurally alerting chemicals, the Salmonella assay showed high sensitivity and low specificity (0.84 and 0.33, respectively). (c) Among the 147 non-alerting chemicals less than 5% were mutagenic, whether they were carcinogens or non-carcinogens (sensitivity 0.04). 相似文献
9.
J Ashby 《Mutation research》1983,115(2):177-213
Some of the probable reasons underlying the observation that not all chemicals shown to be genotoxic in vitro are capable of eliciting tumours in rodents or humans are discussed using appropriate examples. It is suggested that a substantial proportion of the resources currently available for conducting rodent carcinogenicity bioassays should be employed in the short-term evaluation in vivo of some of the many hundreds of chemicals recently defined as genotoxic in vitro, rather than in the protracted evaluation of a few chemicals, often of unknown activity in vitro, for carcinogenicity. A decision tree approach to the evaluation of chemicals for human mutagenic/carcinogenic potential is presented which is at variance with the construction and philosophy of many of the current legislative guidelines. The immediate need for the adoption of one of the available short-term in vivo liver assays, and/or the development of a short-term in vivo rodent assay capable of concomitantly monitoring different genetic end-points in a range of organs or tissues is emphasized. 相似文献
10.