全文获取类型
收费全文 | 55篇 |
免费 | 5篇 |
出版年
2018年 | 1篇 |
2016年 | 1篇 |
2014年 | 1篇 |
2012年 | 1篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2009年 | 3篇 |
2007年 | 2篇 |
2005年 | 3篇 |
2003年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1966年 | 1篇 |
1965年 | 4篇 |
1888年 | 2篇 |
1887年 | 1篇 |
1882年 | 2篇 |
排序方式: 共有60条查询结果,搜索用时 31 毫秒
31.
Inhibition of the peptidyl transferase A-site function by 2'-O-aminoacyloligonucleotides 总被引:2,自引:0,他引:2
New “non-isomerizable” analogs of the 3′-terminus of AA-tRNA, C-A(2′Phe)H, C-A(2′Phe)Me, C-A(2′H)Phe and C-A(2′Me)Phe, were tested as acceptor substrates of ribosomal peptidyl transferase and inhibitors of the peptidyl transferase A-site function. The 3′-O-AA-derivatives were active acceptors of Ac-Phe in the peptidyl transferase reaction, while the 2′-O-AA-derivatives were completely inactive. Both 2′- and 3′-O-AA-derivatives were potent inhibitors of peptidyl transferase catalyzed Ac-Phe transfer to puromycin. The results indicate that although peptidyl transferase exclusively utilizes 3′-O-esters of tRNA as acceptor substrates, its A-site can also recognize the 3′-terminus of 2′-O-AA-tRNA. 相似文献
32.
The distribution of radioactivity among pyrimidine isostichs (or isoplyths) of DNA from 24-h regenerating rat liver was studied with [3H]Thd, [14C]orotate or with inorganic 32Pi. Expression of incorporated radioactivity as log10% of total radioactivity recovered for each of the 11 pyrimidine isostichs detected showed that radioactivity from [3H]Thd was asymmetrically distributed among the isostichs, i.e., 3H radioactivity failed to access regions of DNA yielding lower molecular weight pyrimidine isostichs as efficiently as it accessed regions yielding higher molecular weight pyrimidine isostichs. The thymine (T) content of isostichs exceeded that of cytosine (C), i.e., T/C ratios for the first 10 isostichs averaged 1.43 +/- 0.08 and 1.28 +/- 0.05, depending on the method of analysis; furthermore, the T/C ratio for isostich 1 was significantly higher than ratios for isostichs 2 through 10. Asymmetric distributions of [3H]Thd radioactivity also were seen at 18 or 30 h post-partial hepatectomy. Thus, radioactivity from [3H]Thd, a DNA precursor from the salvage pathway, failed to efficiently access lower molecular weight isostichs despite thymine enrichment, suggesting that thymine moieties were supplied from additional sources. Radioactivity from [14C]orotate accessed lower molecular weight pyrimidine tracts more efficiently than [3H]Thd, but less efficiently than it accessed higher molecular weight isostichs, resulting in an asymmetric distribution of 14C radioactivity. This result suggested that appreciable quantities of thymine and cytosine moieties utilized for DNA synthesis were supplied de novo, but other sources also were utilized. Radioactivity from 32Pi, a de novo precursor, was distributed symmetrically, i.e., the slope among lower molecular weight isostichs increased enough that it was indistinguishable from slopes for intermediate and higher molecular weight isostichs. Since 32P radioactivity among lower molecular weight isostichs reflects appreciable contributions of de novo phosphate moieties from both pyrimidine- and purine-containing deoxynucleoside triphosphates, opportunities for observing contributions of 32P radioactivity from pathways other than the de novo pathways appeared to lie beyond limits of detectability. The distribution of radioactivity from labeled DNA precursors among lower molecular weight pyrimidine tracts (a) indicate that thymine moieties are contributed by both salvage and de novo pathways; (b) support the possibility that cytosine moieties also are contributed by both pathways; and (c) support the 'replitase' concept for channeling dNTPs to replicating forks. 相似文献
33.
Glossop MS Bazin RJ Dack KN Fox DN MacDonald GA Mills M Owen DR Phillips C Reeves KA Ringer TJ Strang RS Watson CA 《Bioorganic & medicinal chemistry letters》2011,21(11):3404-3406
Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2′ subsite within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported. 相似文献
34.
Paul Sirajuddin Sudeep Das Lymor Ringer Olga C. Rodriguez Angiela Sivakumar Yi-Chien Lee Aykut üren Stanley T. Fricke Brian Rood Alpay Ozcan Sean S. Wang Sana Karam Venkata Yenugonda Patricia Salinas Emanuel Petricoin III Michael Pishvaian Michael P. Lisanti Yue Wang Richard Schlegel Bahram Moasser Chris Albanese 《Cell cycle (Georgetown, Tex.)》2012,11(20):3801-3809
The development of new small molecule-based therapeutic drugs requires accurate quantification of drug bioavailability, biological activity and treatment efficacy. Rapidly measuring these endpoints is often hampered by the lack of efficient assay platforms with high sensitivity and specificity. Using an in vivo model system, we report a simple and sensitive liquid chromatography-tandem mass spectrometry assay to quantify the bioavailability of a recently developed novel cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose biological activity is enhanced via dansylation. We developed a rapid organic phase extraction technique and validated wide and functional VMY-1-103 distribution in various mouse tissues, consistent with its enhanced potency previously observed in a variety of human cancer cell lines. More importantly, in vivo MRI and single voxel proton MR-Spectroscopy further established that VMY-1-103 inhibited disease progression and affected key metabolites in a mouse model of hedgehog-driven medulloblastoma. 相似文献
35.
Single-channel currents were recorded from the plasma membrane of white adipocytes of 6-8-week-old male Sprague-Dawley rats. In outside-out patches (high K(+), no Ca(2+) in pipette), a voltage-dependent K-channel (delayed rectifier) with a single-channel conductance (gamma) of 16 pS (24 degrees C) in modified Ringer's was active at a density of 0.5/microm(2). It was blocked by TEA (IC(50)=1.5 mM). A Ca(2+)-activated non-selective cation channel (NSC-channel) appeared at a mean density of 1/microm(2) in inside-out patches ([Ca(2+)](i)=1.2 mM). gamma was 28 pS (24 degrees C). The NSC showed weak voltage dependence and was blocked by mefenamic acid and by internal ATP. In the cell-attached mode spontaneous activity could be blocked reversibly by 100 nM insulin. Noradrenaline (NA, 100 nM) induced a flickering activity of the NSC-channels. Isoproterenol (100 nM) caused activity of the NSC-channel as well. After 1 microM propranolol even 1 microM NA did not induce any activity. The alpha-antagonist phentolamine had no effect on isoproterenol- or on NA-induced currents. The beta(3)-agonists BRL 37344 and BRL 35135A induced activity of the NSC-channel at 100 nM as well. We conclude that white adipocytes express ion channels which are comparable to those in brown adipocytes and that beta-receptor activation opens NSC-channels thus allowing for Na(+) entry into white adipocytes. 相似文献
36.
Purified DNA from the liver of rats, mice, rabbits, and guinea pigs, from guinea pig lymph nodes, from hyperplastic nodules induced in rat liver by feeding with 2-(acetylamino)fluorene, and from Escherichia coli cells was made apurinic by reaction with diphenylamine. After chromatographic separation of pyrimidine tracts (isostichs or isoplyths) according to the number of contiguous pyrimidines, semilog plots of tract frequency vs. the number of contiguous pyrimidines were linear, plots for DNA from several sources differed from one another, and all deviated significantly from randomness. Similar semilog plots for coding sequences among 60 mammalian genomes or 28 rat tissue genomes were intermediate among slopes for isolated DNA. Individual isostichs were hydrolyzed, and their constituent pyrimidine bases were analyzed by high-pressure liquid chromatography. Among isostichs from isolated DNAs, the distribution of Thy and Cyt contents differed markedly from the distribution of 5-methylcytosine (5-Me-Cyt); e.g., although isostich 1 contained 45-49% of 5-Me-Cyt, amounts of Thy or Cyt did not exceed 25%. Semilog plots of normalized values for tract frequency or the content of 5-Me-Cyt vs. isostich number were essentially superimposable; thus, among the first five pyrimidine tracts of a particular tissue or E. coli DNA, the number of tracts per 5-Me-Cyt moiety was essentially constant. The data showed that 5-Me-Cyt and/or dCyd-dGuo dinucleotides have a distribution throughout DNA structure that superimposes the distribution of pyrimidine tract frequency and suggests that regulatory 5-Me-Cyt moieties are principally located at 3' termini of pyrimidine tracts. 相似文献
37.
P L Panzeter J L Etheredge D E Kizer D P Ringer 《Biochemical and biophysical research communications》1987,149(1):27-33
Previous studies in prokaryotes and in eukaryotic cell lines have indicated the possible existence of more than one dTTP pool accessible to DNA synthesis. To investigate this possibility in eukaryotes in vivo, the incorporation of [3H] deoxythymidine into nuclear matrix-attached DNA and intracellular dTTP was examined in regenerating rat liver. The labeling of matrix DNA reached a maximum after a 5 min pulse and then began to rapidly decrease. Conversely, [3H] deoxythymidine incorporation into dTTP began to increase after 5 min and peaked 10 min after injection. Since the peak specific activity for [3H] deoxythymidine incorporation into matrix DNA precedes that into dTTP, there seems to be channeling of exogenous thymidine directly to sites of DNA replication, bypassing existing nucleotide pools. 相似文献
38.
Phosphoamino acids derivatized with 9-fluorenylmethyl chloroformate were separated on an anion-exchange column (Partisil 10 SAX) at pH 3.90 using an isocratic elution with 10.0 mM potassium phosphate, 1.0% tetrahydrofuran, and 55% methanol. Phosphoamino acids were eluted with baseline resolution in the following order: phosphotyrosine, phosphothreonine, and phosphoserine. Each phosphoamino acid was separated from its parent amino acid, dicarboxylic amino acids, sugaramine phosphates, as well as the other common amino acids. The turn-around time from injection to injection was 35 min. The linearity for all three O-linked phosphoamino acids extended from 0.5-1000 pmol and has been shown to be directly applicable to the analysis of isolated phosphoproteins. 相似文献
39.
J H Crosby W C Allsbrook L G Koss C E Bales R Witherington P A Schulte G Hemstreet K Ringer 《Acta cytologica》1991,35(3):263-268
A total of 541 members of a cohort at increased risk for occupational bladder cancer underwent a 33-month program of screening with urine cytology. Selected workers received further urologic study with cystoscopy and bladder biopsies. Eight workers had positive or suspicious cytologic findings. Only one of the eight had a prior history of bladder cancer. Biopsies showed invasive carcinoma and/or nonpapillary carcinoma in situ in five workers in this group, severe atypia in one, and no significant abnormality in two. Of 56 workers who had atypical cytologic findings, 16 had bladder biopsies, which showed atypia of flat urothelium in 11, nonpapillary carcinoma in situ in one, noninfiltrating papillary carcinoma in one, and no significant abnormality in three. The cytologic detection of urothelial abnormalities often required more than a single specimen. Since the cohort in this study may develop more bladder cancers with the passage of time, continued follow-up is indicated. 相似文献
40.
D P Ringer J L Etheredge B L Dalrymple J S Niedbalski 《Biochemical and biophysical research communications》1990,168(1):267-273
Phosphotyrosine, a biologically important protein residue, was investigated for the ability to enhance terbium (Tb3+) fluorescence. Spectroscopic analysis of the Tb3+: phosphotyrosine interaction indicated the development of a new excitation peak at 275 nm and strong Tb+ fluorescence enhancement at 488 and 540 nm that was linear over a range from 0.5 to 100 microM amino acid. Subsequent experiments comparing the ability of phosphotyrosine, phosphothreonine, phosphoserine and 20 other common non-phosphorylated amino acids showed that only phosphotyrosine produced significant Tb3+ fluorescence enhancement. Analysis of various phospho-sugars and nucleotides showed (with the expected exception of GMP) that they produced little or no significant fluorescence enhancement, indicating a further selectiveness for the phosphotyrosine: Tb3+ fluorescence enhancement event. These results establish a basis for the future use of Tb3+ fluorescence enhancement as a unique probe for the investigation of phosphotyrosine residues. 相似文献