全文获取类型
收费全文 | 153篇 |
免费 | 34篇 |
出版年
2021年 | 1篇 |
2019年 | 2篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 2篇 |
2011年 | 4篇 |
2010年 | 2篇 |
2009年 | 7篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 10篇 |
2005年 | 6篇 |
2004年 | 6篇 |
2003年 | 9篇 |
2002年 | 5篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 2篇 |
1986年 | 6篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有187条查询结果,搜索用时 484 毫秒
41.
H Muirhead D A Clayden D Barford C G Lorimer L A Fothergill-Gilmore E Schiltz W Schmitt 《The EMBO journal》1986,5(3):475-481
The complete amino acid sequence of cat muscle pyruvate kinase has been determined and fitted to the 2.6 A resolution electron density map. Residues in the active site region are highly conserved in the cat muscle, chicken muscle, rat liver and yeast enzymes. The enzyme-bound magnesium, which is essential for activity, interacts with the side chain of glutamate-271 and with two main carbonyl groups. Lysine-269 is the probable acid/base catalyst responsible for the interconversion of pyruvate and enolpyruvate. A possible binding site for the essential monovalent cation is proposed. 相似文献
42.
The complete amino acid sequence of cytosolic adenylate kinase (MgATP + AMP----MgADP + ADP) from baker's yeast has been determined. Tryptic and clostripaic cleavage of the protein yielded 27 and 10 fragments, respectively. They were sequenced with either a solid-phase sequencer or a gas-phase sequencer. Alignment of the clostripaic fragments was deduced from the sequence of peptides obtained by endoproteinase Lys-C and cyanogen bromide cleavages. The N-terminus is blocked by an acetyl group as shown by proton magnetic resonance. Carboxypeptidase A digestion of the whole protein showed that the C-terminal sequence is -Lys-Asn, in agreement with the sequence of peptides from tryptic, clostripaic and 2-iodosobenzoic acid cleavages. The enzyme is a monomer of 220 amino acids with Mr 24077. Comparison of the sequence of the cytosolic adenylate kinases from yeast and pig shows 25% identity with highly conserved segments in the putative active-site region of the enzyme. After position 111, however, there is an insertion of 32 residues in the yeast species, similar to the adenylate kinase and the GTP:AMP phosphotransferase from beef heart mitochondria. 相似文献
43.
Structural relationships in the adenylate kinase family 总被引:6,自引:0,他引:6
G E Schulz E Schiltz A G Tomasselli R Frank M Brune A Wittinghofer R H Schirmer 《European journal of biochemistry》1986,161(1):127-132
The sequences of five distantly related adenylate kinases have been aligned. The local conservation of amino acids is discussed in the light of the known three-dimensional structure of one of the enzymes, the cytosolic isoenzyme 1 (AK1) from porcine muscle. The similarity profile outlines clearly the active site in the cleft of the spatial structure of AK1. The alignment reveals further that the enzyme family can be subdivided into small and large variants according to the presence or absence of a particular segment of about 30 residues in the middle of the chain. The extra segments of the large variants are strongly conserved. 相似文献
44.
45.
Four malto-oligosaccharides (dp 2-5), each with a 4,6-O-ethylidene group on the glucosyl unit at the non-reducing terminus, were synthesised and used to prove that the maltose-binding protein (MBP) of E. coli is a closed-groove binder. alpha-D-Glucosylation of 3-azibutyl 1-thio-alpha-D-(6-3H)glucopyranoside yielded a 3H-labelled, photolabile 1-thiomaltoside derivative that was used to chemically modify the binding site of MBP. The 3H-labelled peptide containing 83% of the total radioactivity, which was isolated after tryptic cleavage of the modified MBP and sequenced, is part of the closed end of the MBP groove. 相似文献
46.
High-level ribosomal frameshifting directs the synthesis of IS150 gene products. 总被引:10,自引:0,他引:10
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
IS150 contains two tandem, out-of-phase, overlapping genes, ins150A and ins150B, which are controlled by the same promoter. These genes encode proteins of 19 and 31 kD, respectively. A third protein of 49 kD is a transframe gene product consisting of domains encoded by both genes. Specific -1 ribosomal frameshifting is responsible for the synthesis of the large protein. Expression of ins150B also involves frameshifting. The IS150 frameshifting signals operate with a remarkably high efficiency, causing about one third of the ribosomes to switch frame. All of the signals required for this process are encoded in a 83-bp segment of the element. The heptanucleotide A AAA AAG and a potential stem-loop-forming sequence mark the frameshifting site. Similar sequence elements are found in -1 frameshifting regions of bacterial and retroviral genes. A mutation within the stem-loop sequence reduces the rate of frameshifting by about 80%. Artificial transposons carrying this mutation transpose at a normal frequency, but form cointegrates at a approximately 100-fold reduced rate. 相似文献
47.
Paired sequence difference in ribosomal RNAs: evolutionary and phylogenetic implications 总被引:12,自引:1,他引:11
Ribosomal RNAs have secondary structures that are maintained by internal
Watson-Crick pairing. Through analysis of chordate, arthropod, and plant 5S
ribosomal RNA sequences, we show that Darwinian selection operates on these
nucleotide sequences to maintain functionally important secondary
structure. Insect phylogenies based on nucleotide positions involved in
pairing and the production of secondary structure are incongruent with
those constructed on the basis of positions that are not. Furthermore,
phylogeny reconstruction using these nonpairing bases is concordant with
other, morphological data.
相似文献
48.
Fluorescent glucagon derivatives. I. Synthesis and characterisation of fluorescent glucagon derivatives 总被引:1,自引:0,他引:1
H Heithier L D Ward R C Cantrill H W Klein M J Im G Pollak B Freeman E Schiltz R Peters E J Helmreich 《Biochimica et biophysica acta》1988,971(3):298-306
The synthesis of monofluorescein, monorhodamine, and mono-4-nitrobenz-2-oxa-1,3-diazole (NBD) derivatives of glucagon is reported. The fluorescent groups were introduced by converting tryptophan-25 to 2-thioltryptophan using thiol-specific fluorescent reagents. All derivatives retained the ability to activate adenylate cyclase when compared to glucagon and thus were considered full agonists. IC50 values of 6.8.10(-9), 1.7.10(-8), 1.8.10(-8) and 5.4.10(-9) M were measured in rat liver membranes for NBD-, fluorescein-, rhodamine-Trp25-glucagon and native glucagon, respectively. From the IC50 values Kd values of 2.16.10(-9), 4.10(-9), 2.10(-9) and 1.72.10(-9) M were calculated for the binding of NBD-, fluorescein-, rhodamine-Trp25-glucagon and native glucagon, respectively. The highest quantum yield (0.18) of the monomer derivatives was obtained with fluorescein-Trp25-glucagon in phosphate-buffered saline (pH 7.4). Difluorescein-glucagon was also prepared by reacting the amino groups of histidine-1 and lysine-12 with fluorescein isothiocyanate and dimer derivatives were prepared using fluorescein-labelled 2-thiolTrp25-glucagon. Difluorescein-glucagon bound only weakly to glucagon receptors and displayed antagonist properties. The dimer derivative formed from two difluorescein-2-thiolTrp25-glucagon molecules had similar poor binding qualities, whereas the dimer formed from difluorescein-2-thiolTrp25-glucagon and 2-thiolTrp25-glucagon exhibited, at low concentrations, properties similar to monofluorescein-glucagon. Both dimer derivatives were only sparingly soluble in aqueous medium. Specific binding of fluorescein-Trp25-glucagon and difluorescein-glucagon to rat hepatocytes was followed using flow cytometry. 相似文献
49.
50.
Discovery of a novel class of potent and selective tetrahydroindazole-based sigma-1 receptor ligands
Iredia D. Iyamu Wei Lv Neha Malik Rama K. Mishra Gary E. Schiltz 《Bioorganic & medicinal chemistry》2019,27(9):1824-1835
The sigma-1 and sigma-2 receptors have been shown to play important roles in CNS diseases, cancer, and other disorders. These findings suggest that targeting these proteins with small-molecule modulators may be of important therapeutic value. Here we report the development of a new class of tetrahydroindazoles that are highly potent and selective ligands for sigma-1. Molecular modeling was used to rationalize the observed structure-activity relationships and identify key interactions responsible for increased potency of the optimized compounds. Assays for solubility and microsomal stability showed this series possesses favorable characteristics and is amenable to further therapeutic development. The compounds described herein will be useful in the development of new chemical probes for sigma-1 and to aid in future work therapeutically targeting this protein. 相似文献