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131.
High frequency hearing loss correlated with mutations in the GJB2 gene 总被引:18,自引:0,他引:18
Wilcox SA Saunders K Osborn AH Arnold A Wunderlich J Kelly T Collins V Wilcox LJ McKinlay Gardner RJ Kamarinos M Cone-Wesson B Williamson R Dahl HH 《Human genetics》2000,106(4):399-405
Genetic hearing impairment affects approximately 1/2000 live births. Mutations in one gene, GJB2, coding for connexin 26 cause 10%-20% of all genetic sensorineural hearing loss. Mutation analysis in the GJB2 gene and audiology were performed on 106 families presenting with at least one child with congenital hearing loss. The families were recruited from a hospital-based multidisciplinary clinic, which functions to investigate the aetiology of sensorineural hearing loss in children and which serves an ethnically diverse population. In 74 families (80 children), the aetiology was consistent with non-syndromic recessive hearing loss. Six different connexin 26 mutations, including one novel mutation, were identified. We show that GJB2 mutations cause a range of phenotypes from mild to profound hearing impairment and that loss of hearing in the high frequency range (4000-8000 Hz) is a characteristic feature in children with molecularly diagnosed connexin 26 hearing impairment. We also demonstrate that this type of audiology and high frequency hearing loss is found in a similar-sized group of deaf children in whom a mutation could only be found in one of the connexin 26 alleles, suggesting connexin 26 involvement in the aetiology of hearing loss in these cases. In our study of the M34T mutation, only compound heterozygotes exhibited hearing loss, suggesting autosomal recessive inheritance. 相似文献
132.
van Kranenburg R Golic N Bongers R Leer RJ de Vos WM Siezen RJ Kleerebezem M 《Applied and environmental microbiology》2005,71(3):1223-1230
Lactobacillus plantarum WCFS1 harbors three plasmids, pWCFS101, pWCFS102, and pWCFS103, with sizes of 1,917, 2,365, and 36,069 bp, respectively. The two smaller plasmids are of unknown function and contain replication genes that are likely to function via the rolling-circle replication mechanism. The host range of the pWCFS101 replicon includes Lactobacillus species and Lactococcus lactis, while that of the pWCFS102 replicon also includes Carnobacterium maltaromaticum and Bacillus subtilis. The larger plasmid is predicted to replicate via the theta-type mechanism. The host range of its replicon seems restricted to L. plantarum. Cloning vectors were constructed based on the replicons of all three plasmids. Plasmid pWCFS103 was demonstrated to be a conjugative plasmid, as it could be transferred to L. plantarum NC8. It confers arsenate and arsenite resistance, which can be used as selective markers. 相似文献
133.
Teusink B van Enckevort FH Francke C Wiersma A Wegkamp A Smid EJ Siezen RJ 《Applied and environmental microbiology》2005,71(11):7253-7262
On the basis of the annotated genome we reconstructed the metabolic pathways of the lactic acid bacterium Lactobacillus plantarum WCFS1. After automatic reconstruction by the Pathologic tool of Pathway Tools (http://bioinformatics.ai.sri.com/ptools/), the resulting pathway-genome database, LacplantCyc, was manually curated extensively. The current database contains refinements to existing routes and new gram-positive bacterium-specific reactions that were not present in the MetaCyc database. These reactions include, for example, reactions related to cell wall biosynthesis, molybdopterin biosynthesis, and transport. At present, LacplantCyc includes 129 pathways and 704 predicted reactions involving some 670 chemical species and 710 enzymes. We tested vitamin and amino acid requirements of L. plantarum experimentally and compared the results with the pathways present in LacplantCyc. In the majority of cases (32 of 37 cases) the experimental results agreed with the final reconstruction. LacplantCyc is the most extensively curated pathway-genome database for gram-positive bacteria and is open to the microbiology community via the World Wide Web (www.lacplantcyc.nl). It can be used as a reference pathway-genome database for gram-positive microbes in general and lactic acid bacteria in particular. 相似文献
134.
Structure and stability of gamma-crystallins. I. Spectroscopic evaluation of secondary and tertiary structure in solution 总被引:2,自引:0,他引:2
The three major bovine gamma-crystallin fractions (gamma-II, gamma-III and gamma-IV) are known to have closely related (80-90%) amino acid sequences and three-dimensional folding of the polypeptide backbone. Their chiroptical and emission properties, as measured by circular dichroism (CD) and fluorescence, are now shown to differ distinctly. The far-ultraviolet CD spectra indicate that all three gamma-crystallins have predominantly beta-sheet conformation (45-60%) with only subtle differences in secondary structure. The fluorescence emission maxima of gamma-II, gamma-III and gamma-IV, due to the four tryptophan residues, appear at 324, 329 and 334 nm, respectively, suggesting that tryptophan residues are buried in environments of decreasing hydrophobicity. Corresponding differences in quantum yield may be due to fluorescence quenching by neighboring sulfur-containing residues. Titratable tyrosines are maximal for gamma-III, as manifested from difference absorption spectra at alkaline pH. The near-ultraviolet CD spectra differ in position, magnitude and sign of tryptophan and tyrosine transitions. In addition, a characteristic CD maximum at 235 nm, presumably due to tyrosine-tyrosine exciton interactions, differs in magnitude for each gamma-crystallin. This study shows that the environment and interactions of the aromatic residues of the individual gamma-crystallin fractions are quite different. These variations in tertiary structure may be significant, in terms of stability of gamma-crystallins towards aggregation and denaturation, for understanding lens transparency and cataract formation in general. 相似文献
135.
136.
137.
Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. 总被引:18,自引:6,他引:12
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J R van der Meer J Polman M M Beerthuyzen R J Siezen O P Kuipers W M De Vos 《Journal of bacteriology》1993,175(9):2578-2588
Biosynthesis of the lantibiotic peptide nisin by Lactococcus lactis NIZO R5 relies on the presence of the conjugative transposon Tn5276 in the chromosome. A 12-kb DNA fragment of Tn5276 including the nisA gene and about 10 kb of downstream DNA was cloned in L. lactis, resulting in the production of an extracellular nisin precursor peptide. This peptide reacted with antibodies against either nisin A or the synthetic leader peptide, suggesting that it consisted of a fully modified nisin with the nisin leader sequence still attached to it. This structure was confirmed by N-terminal sequencing and 1H-nuclear magnetic resonance analysis of the purified peptide. Deletion studies showed that the nisR gene is essential for the production of this intermediate. The deduced amino acid sequence of the nisR gene product indicated that the protein belongs to the family of two-component regulators. The deduced amino acid sequence of NisP, the putative product of the gene upstream of nisR, showed an N-terminal signal sequence, a catalytic domain with a high degree of similarity to those of subtilisin-like serine proteases, and a putative C-terminal membrane anchor. Cell extracts of Escherichia coli overexpressing nisP were able to cleave the nisin precursor peptide, producing active, mature nisin. A similar activation was obtained with whole cells but not with membrane-free extracts of L. lactis strains carrying Tn5276 in which the nisA gene had been inactivated. The results indicate that the penultimate step in nisin biosynthesis is secretion of precursor nisin without cleavage of the leader peptide, whereas the last step is the cleavage of the leader peptide sequence from the fully maturated nisin peptide. 相似文献
138.
139.
Molecular phylogenetics of Stenodermatini bat genera: congruence of data from nuclear and mitochondrial DNA 总被引:2,自引:1,他引:1
Van den Bussche RA; Baker RJ; Wichman HA; Hamilton MJ 《Molecular biology and evolution》1993,10(5):944-959
Within the tribe Stenodermatini the systematics of the complex of species
allied with the genus Artibeus has generated several alternative
phylogenetic hypotheses. The most recent treatment recognized four genera
(Artibeus, Dermanura, Enchisthenes, and Koopmania) and suggested that the
most recent common ancestor of these four genera would include the common
ancestor of all other currently recognized Stenodermatini genera except
Sturnira. To test this hypothesis, we examined an EcoRI-defined nuclear
satellite DNA repeat and 402 bp of DNA sequence variation from the
mitochondrial cytochrome b gene. Phylogenetic conclusions based on Southern
blot analyses, in situ hybridization, and mitochondrial DNA sequence data
indicate that Enchisthenes is not closely related to Dermanura, Artibeus,
or Koopmania and that Dermanura, Artibeus, and Koopmania shared a common
ancestor after diverging from the remainder of the Stenodermatini. If our
conclusions are correct, then justification for recognizing Dermanura and
Koopmania as generically distinct from Artibeus must be based on the
magnitude of difference that distinguishes each rather than on the
conclusion that to place them as congeneric with Artibeus creates a
paraphyletic taxon.
相似文献
140.