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81.
82.
Role of cryptic genes in microbial evolution 总被引:24,自引:1,他引:23
Cryptic genes are phenotypically silent DNA sequences, not normally
expressed during the life cycle of an individual. They may, however, be
activated in a few individuals of a large population by mutation,
recombination, insertion elements, or other genetic mechanisms. A
consideration of the microbial literature concerning biochemical evolution,
physiology, and taxonomy provides the basis for a hypothesis of microbial
adaptation and evolution by mutational activation of cryptic genes.
Evidence is presented, and a mathematical model is derived, indicating that
powerful and biologically important mechanisms exist to prevent the loss of
cryptic genes. We propose that cryptic genes persist as a vital element of
the genetic repertoire, ready for recall by mutational activation in future
generations. Cryptic genes provide a versatile endogenous genetic reservoir
that enhances the adaptive potential of a species by a mechanism that is
independent of genetic exchange.
相似文献
83.
Characterization of the Critical Amino Acids of an Aspergillus parasiticus Cytochrome P-450 Monooxygenase Encoded by ordA That Is Involved in the Biosynthesis of Aflatoxins B1, G1, B2, and G2 总被引:1,自引:0,他引:1 下载免费PDF全文
Jiujiang Yu Perng-Kuang Chang Kenneth C. Ehrlich Jeffrey W. Cary Beverly Montalbano John M. Dyer Deepak Bhatnagar Thomas E. Cleveland 《Applied microbiology》1998,64(12):4834-4841
The conversion of O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin to aflatoxins B1, G1, B2, and G2 requires a cytochrome P-450 type of oxidoreductase activity. ordA, a gene adjacent to the omtA gene, was identified in the aflatoxin-biosynthetic pathway gene cluster by chromosomal walking in Aspergillus parasiticus. The ordA gene was a homolog of the Aspergillus flavus ord1 gene, which is involved in the conversion of OMST to aflatoxin B1. Complementation of A. parasiticus SRRC 2043, an OMST-accumulating strain, with the ordA gene restored the ability to produce aflatoxins B1, G1, B2, and G2. The ordA gene placed under the control of the GAL1 promoter converted exogenously supplied OMST to aflatoxin B1 in Saccharomyces cerevisiae. In contrast, the ordA gene homolog in A. parasiticus SRRC 2043, ordA1, was not able to carry out the same conversion in the yeast system. Sequence analysis revealed that the ordA1 gene had three point mutations which resulted in three amino acid changes (His-400→Leu-400, Ala-143→Ser-143, and Ile-528→Tyr-528). Site-directed mutagenesis studies showed that the change of His-400 to Leu-400 resulted in a loss of the monooxygenase activity and that Ala-143 played a significant role in the catalytic conversion. In contrast, Ile-528 was not associated with the enzymatic activity. The involvement of the ordA gene in the synthesis of aflatoxins G1, and G2 in A. parasiticus suggests that enzymes required for the formation of aflatoxins G1 and G2 are not present in A. flavus. The results showed that in addition to the conserved heme-binding and redox reaction domains encoded by ordA, other seemingly domain-unrelated amino acid residues are critical for cytochrome P-450 catalytic activity. The ordA gene has been assigned to a new cytochrome P-450 gene family named CYP64 by The Cytochrome P450 Nomenclature Committee. 相似文献
84.
Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species 总被引:3,自引:0,他引:3
The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via
developmentally regulated alternative pre-mRNA splicing. In larval muscle
and tubular and abdominal muscles of adults, all of the six exons are
included in the spliced mRNA, whereas, in the fibrillar indirect flight
muscle of adult, exon 5 is excluded from the mRNA. We show that this
tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is
conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and
sequencing of the Mlc1 genes from these three other Drosophila species have
revealed that the overall organization of the genes is identical and that
the genes have maintained a very high level of sequence identity within the
coding region. Pairwise amino acid identities are 94%-99%, and there are no
charge changes among the proteins. Total nucleotide divergence within the
coding region of the four genes supports the accepted genealogy of these
species, but the data indicate a significantly higher rate of amino acid
replacement in the branch leading to D. pseudoobscura. A comparison of
nucleotide substitutions in the coding portions of exon 5 and exon 6, which
encode the alternative carboxyl termini of the two MLC1 isoforms, suggests
that exon 5 is subject to greater evolutionary constraints than is exon 6.
In addition to the coding sequences, there is significant sequence
conservation within the 5' and 3' noncoding DNA and two of the introns,
including one that flanks exon 5. These regions are candidates for cis-
regulatory elements. Our results suggest that evolutionary constraints are
acting on both the coding and noncoding sequences of the Mlc1 gene to
maintain proper expression and function of the two MLC1 polypeptides.
相似文献
85.
Sequence evolution and phylogenetic signal in control-region and cytochrome b sequences of rainbow fishes (Melanotaeniidae) 总被引:3,自引:0,他引:3
The nucleotide sequences of segments of the cytochrome b gene (351 bp), the
tRNA(Pro) gene (49 bp), and the control region (approximately 313 bp) of
mitochondrial DNA were obtained from 26 fish representing different
populations and species of Melanotaenia and one species of Glossolepis,
freshwater rainbow fishes confined to Australia and New Guinea. The purpose
was to investigate relative rates and patterns of sequence evolution.
Overall levels of divergence were similar for the cytochrome b and tRNA
control-region sequences, both ranging from < 1% within subspecies to
15%-19% between genera. However, the patterns of sequence evolution
differed. For the cytochrome b gene, transitions consistently exceeded
transversions, the bias ranging from 4.2:1 to 2:1, depending on the level
of sequence divergence. However, in the control-region sequence, a bias
toward transitions (2:1) was observed only in comparisons between very
similar sequences, and transversions outnumbered transitions in comparisons
of divergent sequences. Graphic comparisons suggested that the control
region was saturated for transitions at relatively low levels of sequence
divergence but accumulated transversions at a greater rate than did the
cytochrome b sequence. These distinct patterns of base substitution are
associated with differences in A+T content, which is 70% for the tRNA
control- region segment versus 50% for cytochrome b. A test for skewness in
the distribution of lengths of random trees indicated that both segments
contained phylogenetic signal. Parsimony analyses of the data from the two
regions, with or without weighting schemes appropriate to the respective
patterns of sequence evolution, identified the same five groupings of
sequences, but the relationships among the groups differed. However, in
most cases the branches uniting different combinations of groups were
poorly supported, and the differences among topologies were insignificant.
Considering the observed patterns of base substitution and the results of
the phylogenetic analyses, we deduce that both the control region and
cytochrome b are appropriate for population genetic studies but that the
control region is less effective than cytochrome b for resolving
relationships among divergent lineages of rainbow fishes.
相似文献
86.
An ethidium bromide-agarose plate assay for the nonradioactive detection of cDNA synthesis 总被引:2,自引:0,他引:2
Ethidium bromide was used to determine the success of cDNA synthesis reactions. Since ethidium bromide in agarose can be used to quantitate RNA and DNA, conditions under which the greater fluorescence of double-stranded DNA (dsDNA) is utilized were devised to assay dsDNA synthesis from mRNA. Ethidium bromide at 5 micrograms/ml in agarose allowed quantitative detection of cDNA in the range of 0.03 to 0.0015 microgram. Sodium dodecyl sulfate had an adverse effect on the measurement of cDNA. Subsequent cDNA analysis by alkaline gel electrophoresis and staining in 5 micrograms/ml ethidium bromide allowed accurate and rapid sizing of cDNA and required only 0.1-0.05 microgram cDNA. 相似文献
87.
Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia 总被引:1,自引:0,他引:1
Rossi F Garavaglia S Montalbano V Walsh MA Rizzi M 《The Journal of biological chemistry》2008,283(6):3559-3566
Kynurenic acid is an endogenous neuroactive compound whose unbalancing is involved in the pathogenesis and progression of several neurological diseases. Kynurenic acid synthesis in the human brain is sustained by the catalytic activity of two kynurenine aminotransferases, hKAT I and hKAT II. A wealth of pharmacological data highlight hKAT II as a sensible target for the treatment of neuropathological conditions characterized by a kynurenic acid excess, such as schizophrenia and cognitive impairment. We have solved the structure of human KAT II by means of the single-wavelength anomalous dispersion method at 2.3-A resolution. Although closely resembling the classical aminotransferase fold, the hKAT II architecture displays unique features. Structural comparison with a prototypical aspartate aminotransferase reveals a novel antiparallel strand-loop-strand motif that forms an unprecedented intersubunit beta-sheet in the functional hKAT II dimer. Moreover, the N-terminal regions of hKAT II and aspartate aminotransferase appear to have converged to highly similar although 2-fold symmetry-related conformations, which fulfill the same functional role. A detailed structural comparison of hKAT I and hKAT II reveals a larger and more aliphatic character to the active site of hKAT II due to the absence of the aromatic cage involved in ligand binding in hKAT I. The observed structural differences could be exploited for the rational design of highly selective hKAT II inhibitors. 相似文献
88.
Thiopyrano[2,3-e]indol-2-ones: angelicin heteroanalogues with potent photoantiproliferative activity
Barraja P Diana P Montalbano A Carbone A Cirrincione G Viola G Salvador A Vedaldi D Dall'acqua F 《Bioorganic & medicinal chemistry》2008,16(22):9668-9683
A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50) values at submicromolar level. This latter photoinduced a massive apoptosis and a remarkable photodamage to lipids and proteins. Although it did not intercalate DNA, it was able to cause photooxidation of DNA bases. 相似文献
89.
Barraja P Diana P Lauria A Montalbano A Almerico AM Dattolo G Cirrincione G 《Bioorganic & medicinal chemistry》2005,13(2):295-300
Eight derivatives of the new ring system [1,2,3,5]tetrazino[5,4-a]indole-4-one 7, were synthesised in good yields by reaction of 2-diazoindoles with alkyl or aryl isocyanates. Compounds 7 were screened at National Cancer Institute (NCI) for their activity against a panel of approximately 60 human tumour cell lines. Some of them showed antiproliferative activity having generally GI50 in the micromolar range. The most sensitive cell lines were SF-295, SNB-75 and SF-539 of the CNS cancer sub-panel, SR of the leukaemia sub-panel, UACC-62 of the melanoma sub-panel and OVCAR-4 of the ovarian cancer sub-panel. 相似文献
90.