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81.
Chun-Chi Liu Chin-Chung Lin Ker-Chau Li Wen-Shyen E Chen Jiun-Ching Chen Ming-Te Yang Pan-Chyr Yang Pei-Chun Chang Jeremy JW Chen 《BMC bioinformatics》2007,8(1):164
Background
Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos. 相似文献82.
3-Carboxy-cis,cis-muconate lactonizing enzyme from Neurospora crassa: an alternate cycloisomerase motif. 下载免费PDF全文
3-Carboxy-cis,cis-muconate lactonizing enzyme (CMLE; EC 5.5.1.5) from Neurospora crassa catalyzes the reversible gamma-lactonization of 3-carboxy-cis,cis-muconate by a syn-1,2 addition-elimination reaction. The stereochemical and regiochemical course of the reaction is (i) opposite that of CMLE from Pseudomonas putida (EC 5.5.1.2) and (ii) identical to that of cis,cis-muconate lactonizing enzyme (MLE; EC 5.5.1.1) from P. putida. In order to determine the mechanistic and evolutionary relationships between N. crassa CMLE and the procaryotic cycloisomerases, we have purified CMLE from N. crassa to homogeneity and determined its nucleotide sequence from a cDNA clone isolated from a p-hydroxybenzoate-induced N. crassa cDNA library. The deduced amino acid sequence predicts a protein of 41.2 kDa (365 residues) which does not exhibit sequence similarity with any of the bacterial cycloisomerases. The cDNA encoding N. crassa CMLE was expressed in Escherichia coli, and the purified recombinant protein exhibits physical and kinetic properties equivalent to those found for the isolated N. crassa enzyme. We also report that N. crassa CMLE possesses substantially reduced yet significant levels of MLE activity with cis,cis-muconate and, furthermore, does not appear to be dependent on divalent metals for activity. These data suggest that the N. crassa CMLE may represent a novel eucaryotic motif in the cycloisomerase enzyme family. 相似文献
83.
Basolateral K channels in an insect epithelium. Channel density, conductance, and block by barium 下载免费PDF全文
K channels in the basolateral membrane of insect hindgut were studied using current fluctuation analysis and microelectrodes. Locust recta were mounted in Ussing-type chambers containing Cl-free saline and cyclic AMP (cAMP). A transepithelial K current was induced by raising serosal [K] under short-circuit conditions. Adding Ba to the mucosal (luminal) side under these conditions had no effect; however, serosal Ba reversibly inhibited the short-circuit current (Isc), increased transepithelial resistance (Rt), and added a Lorentzian component to power density spectra of the Isc. A nonlinear relationship between corner frequency and serosal [Ba] was observed, which suggests that the rate constant for Ba association with basolateral channels increased as [Ba] was elevated. Microelectrode experiments revealed that the basolateral membrane hyperpolarized when Ba was added: this change in membrane potential could explain the nonlinearity of the 2 pi fc vs. [Ba] relationship if external Ba sensed about three-quarters of the basolateral membrane field. Conventional microelectrodes were used to determine the correspondence between transepithelially measured current noise and basolateral membrane conductance fluctuations, and ion-sensitive microelectrodes were used to measure intracellular K activity (acK). From the relationship between the net electrochemical potential for K across the basolateral membrane and the single channel current calculated from noise analysis, we estimate that the conductance of basolateral K channels is approximately 60 pS, and that there are approximately 180 million channels per square centimeter of tissue area. 相似文献
84.
Overview of microbial biofilms 总被引:13,自引:0,他引:13
Dr JW Costerton 《Journal of industrial microbiology & biotechnology》1995,15(3):137-140
As the success of this two-issue special section of the Journal of Industrial Microbiology attests, the study of microbial biofilms is truly burgeoning as the uniqueness and the importance of this mode of growth is increasingly recognized. Because of its universality the biofilm concept impacts virtually all of the subdivisions of Microbiology (including Medical, Dental, Agricultural, Industrial and Environmental) and these two issues incorporate contributions from authors in all of these disciplines. Some time ago we reasoned that bacteria cannot possibly be aware (sic) of their precise location, in terms of this spectrum of anthrocentric subspecialties, and that their behavior must be dictated by a standard set of phenotypic responses to environmental conditions in what must seem to them (sic) to be a continuum of very similar aquatic ecosystems. In this overview I will, therefore, stress the common features of microbial biofilms that we should bear in mind as we use this simple universal concept to seek to understand bacterial behavior in literally hundreds of aquatic ecosystems traditionally studied by dozens of subspecies of microbiologists reared in sharply different scientific and academic conventions. 相似文献
85.
Prolyl peptidases: a serine protease subfamily with high potential for drug discovery 总被引:8,自引:0,他引:8
Much attention has recently been given to a class of proteases that cleave proteins and peptides after proline residues. This class includes dipeptidyl peptidase IV (DPP IV; also termed CD26), fibroblast activation protein alpha (FAP; seprase), DPP7 (DPP II; quiescent cell proline dipeptidase), DPP8, DPP9, and prolyl carboxypeptidase (PCP; angiotensinase C). More distant members include prolyl oligopeptidase (POP; post proline cleaving enzyme) and acylaminoacylpeptidase (AAP; acylpeptide hydrolase). The DPPs and related proteins contain both membrane-bound and soluble members and span a broad range of expression patterns, tissue distributions and compartmentalization. These proteins have important roles in regulation of signaling by peptide hormones, and are emerging targets for diabetes, oncology and other indications. 相似文献
86.
Restriction-map variation with the yellow-achaete-scute region in five populations of Drosophila melanogaster 总被引:9,自引:0,他引:9
It has been proposed that the degree of recombination for a genomic region
will affect the level of both nucleotide heterozygosity and the density of
transposable elements. Both features of genomic diversity have been
examined in a number of recent reports for regions undergoing relatively
normal levels of recombination in Drosophila melanogaster. In this study
the genomic variation associated with yellow-achaete- scute loci located at
the tip of the X chromosome is examined by six- cutter restriction mapping.
In this region, as usual for regions adjacent to telomeres, crossing-over
is dramatically reduced, and published studies of visible mutants indicate
extremely little restriction-map variation. Eight six-cutter restriction
endonucleases were used to locate sequence variation in 14- and 16.5-kb
regions in 109 lines sampled from North America, Africa, and Europe. The
overall level of heterozygosity is estimated as 0.29%. Nine large
insertions, all presumed to be transposable elements, were observed.
Base-pair heterozygosity appears to be reduced compared with regions having
normal levels of recombination. The estimated heterozygosity is much higher
than reported in earlier studies of restriction-map variation among visible
mutations in the complex. The incidence of large insertions is not elevated
compared with that in other regions of the genome. This suggests that
asymmetric synapsis and exchange is not an important mechanism for the
elimination of transposable elements.
相似文献
87.
The ability of glyoxalase I to isomerize both diastereomeric thiohemiacetals formed between glutathione and alpha-ketoaldehydes has been probed with stereochemically "locked" substrate analogues. Both (R)- and (S)-glutathiolactaldehyde (5 and 5') were unambiguously synthesized by employing the Sharpless epoxidation procedure as a key step. In the presence of human erythrocyte glyoxalase I, high-field 1H NMR analysis reveals that the R and S isomers (approximately 20 mM) are both converted to glutathiohydroxyacetone at rates of 0.8 and 0.4 s-1, respectively. This reaction is characterized by a nonstereospecific proton abstraction followed by a partially shielded proton transfer to the si face of the cis-enediol intermediate. Glyoxalase I catalyzes the exchange of the pro-S proton of glutathiohydroxyacetone with solvent deuterium. Glutathiohydroxyacetone was found to be a good competitive inhibitor of the normal glyoxalase I reaction (KI = 1.46 mM), suggesting that the slow processing rate of these compounds with respect to the normal thiohemiacetals is not due to poor binding. The results are consistent with a nonstereospecific proton abstraction and a stereospecific reprotonation at contiguous substrate carbons. 相似文献
88.
Yi Hu Emme C.K. Lin Lan M. Pham Julia Cajica Christopher M. Amantea Eric Okerberg Heidi E. Brown Allister Fraser Lingling Du Yasushi Kohno Junichi Ishiyama John W. Kozarich Kevin R. Shreder 《Bioorganic & medicinal chemistry letters》2013,23(5):1553-1556
AX10479, the phenyl amide of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid, was identified as a Zn2+-dependent, 27 nM inhibitor of human plasma Lp-PLA2. Structure–activity relationship studies focused on the AX10479 2-phenylamide group identified equipotent cycloaliphatic amides, an enantioselective preference for chiral amides, and phenyl substitution patterns (e.g., 2-methyl-3-fluoro) that increased potency. 相似文献
89.
Effects of hypoxanthine substitution on bleomycin-mediated DNA strand degradation in DNA-RNA hybrids. 下载免费PDF全文
We have reported on the differences in site-specific cleavage between DNA and DNA-RNA hybrids by various prototypic DNA cleavers (accompanying paper). In the case of bleomycin (BLM), degradation at 5'-GC-3'sites was suppressed relative to the same sequence in double-stranded DNA, while 5'-GT-3' damage remained constant. We now present results of our further investigation on the chemical and conformational factors that contribute to BLM-mediated DNA strand cleavage of DNA-RNA hybrids. Substitution of guanine by hypoxanthine on the RNA strand of hybrids resulted in a significant enhancement of 5'-GC-3' site damage on the DNA strand relative to double-stranded DNA, thus reversing the suppression noted at these sites. Additionally, 5'-AT-3' sites, which are damaged significantly more in the hybrid than in DNA, exhibit decreased product formation when hypoxanthine is present on the RNA strand of hybrids. However, when hypoxanthine is substituted for guanine on the DNA strand (a GC cleavage site becomes IC), 5'-IT-3' and 5'-IC-3' site cleavage is almost completely suppressed, whereas AT site cleavage is dramatically enhanced. The priority in metallobleomycin site-specific cleavage of hybrids changes with hypoxanthine substitution: the cleavage priority is AT > GT > GC in native hybrid; GC > GT > AT in hybrids substituted with hypoxanthine in the RNA strand; AT >> GT approximately GC in hybrids substituted with hypoxanthine in the DNA strand. The results of kinetic isotope effect studies on BLM cleavage are presented and, in most cases, the values are larger for the hypoxanthine-substituted hybrid. The results suggest that the 2-amino groups of guanine residues on both strands of the nucleic acid play an important role in modulation of the binding and cleavage specificity of BLM. 相似文献
90.
Liu Y Wu J Weissig H Betancort JM Gai WZ Leventhal PS Patricelli MP Samii B Szardenings AK Shreder KR Kozarich JW 《Bioorganic & medicinal chemistry letters》2008,18(22):5955-5958
The synthesis and biochemical characterization of AX4697, a fluorescent, bisindolylmaleimide-derived probe for PKCalpha and beta, is described. AX4697 was able to quantify changes in PKC expression in drug-treated Jurkat cells and was shown to covalently label PKCalpha on C619, a residue that sits just outside the active site. 相似文献