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1.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
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2.
Proline excretion from proline overproducing strains of E. coli K12 has been studied as a model chemical production system. We have isolated proline overproducing mutants of E. coli and have shown that uncontrolled synthesis is not sufficient to cause excretion of this amino acid. An episomal mutation causing proline over production has been introduced into a series of otherwise isogenic strains that bear well defined, chromosomal lesions affecting the active uptake and catabolism of L-proline. A syntropism test reveals that L-proline is excreted by overproducing strains only if transport and/or catabolism are impaired. Dansyl derivatization and chromatographic analysis of culture supernatants shows that proline is the only amino acid excreted. Batch cultures of an excreting strain in an amino acid production medium yield culture supernatants containing 1 g proline/L, whereas no proline is detectable in supernatants derived from cultures of an overproducing strain with normal transport and catabolic activities. These data reveal that genetic lesions eliminating active uptake can be used to specifically enhance metabolite excretion. 相似文献
3.
Assignment of orthologous relationships among mammalian alpha-globin genes by examining flanking regions reveals a rapid rate of evolution 总被引:1,自引:0,他引:1
In order to study the relationships among mammalian alpha-globin genes, we
have determined the sequence of the 3' flanking region of the human alpha 1
globin gene and have made pairwise comparisons between sequenced
alpha-globin genes. The flanking regions were examined in detail because
sequence matches in these regions could be interpreted with the least
complication from the gene duplications and conversions that have occurred
frequently in mammalian alpha-like globin gene clusters. We found good
matches between the flanking regions of human alpha 1 and rabbit alpha 1,
human psi alpha 1 and goat I alpha, human alpha 2 and goat II alpha, and
horse alpha 1 and goat II alpha. These matches were used to align the
alpha-globin genes in gene clusters from different mammals. This alignment
shows that genes at equivalent positions in the gene clusters of different
mammals can be functional or nonfunctional, depending on whether they
corrected against a functional alpha-globin gene in recent evolutionary
history. The number of alpha-globin genes (including pseudogenes) appears
to differ among species, although highly divergent pseudogenes may not have
been detected in all species examined. Although matching sequences could be
found in interspecies comparisons of the flanking regions of alpha- globin
genes, these matches are not as extensive as those found in the flanking
regions of mammalian beta-like globin genes. This observation suggests that
the noncoding sequences in the mammalian alpha-globin gene clusters are
evolving at a faster rate than those in the beta-like globin gene clusters.
The proposed faster rate of evolution fits with the poor conservation of
the genetic linkage map around alpha-globin gene clusters when compared to
that of the beta-like globin gene clusters. Analysis of the 3' flanking
regions of alpha-globin genes has revealed a conserved sequence
approximately 100-150 bp 3' to the polyadenylation site; this sequence may
be involved in the expression or regulation of alpha-globin genes.
相似文献
4.
Timothy A. Stammers René Coulombe Martin Duplessis Gulrez Fazal Alexandre Gagnon Michel Garneau Sylvie Goulet Araz Jakalian Steven LaPlante Jean Rancourt Bounkham Thavonekham Dominik Wernic George Kukolj Pierre L. Beaulieu 《Bioorganic & medicinal chemistry letters》2013,23(24):6879-6885
Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar. 相似文献
5.
Transplacement mutagenesis: a novel in situ mutagenesis system using phage-plasmid recombination 下载免费PDF全文
Site-specific mutagenesis provides the ability to alter DNA with precision so that the function of any given gene can be more fully understood. Several methods of in vitro mutagenesis are time-consuming and imprecise, requiring the subcloning and sequencing of products. Here we describe a rapid, high fidelity method of in situ mutagenesis in bacteriophage lambda using transplacement. Using this method, mutations are transferred from oligonucleotides to target phages using a plasmid interface. A small (50 bp) homology region bearing a centred point mutation is generated from oligonucleotides and subcloned into a transplacement plasmid bearing positive and negative phage selectable markers. Following a positive/negative selection cycle of integrative recombination and excision, the point mutation is transferred precisely from plasmid to phage in a subset ( approximately 25-50%) of recombinants. As the fidelity of both oligonucleotide synthesis and phage-plasmid recombination is great, this approach is extremely reliable. Using transplacement, point mutations can be accurately deposited within large phage clones and we demonstrate the utility of this technique in the construction of gene targeting vectors in bacteriophages. 相似文献
6.
Rancourt RC Tai S King M Heltshe SL Penvari C Accurso FJ White CW 《American journal of physiology. Lung cellular and molecular physiology》2004,286(5):L931-L938
The persistent and viscous nature of airway secretions in cystic fibrosis (CF) disease leads to airway obstruction, opportunistic infection, and deterioration of lung function. Thioredoxin (Trx) is a protein disulfide reductase that catalyzes numerous thiol-dependent cellular reductive processes. To determine whether Trx can alter the rheological properties of mucus, sputum obtained from CF patients was treated with TRX and its reducing system (0.1 microM thioredoxin reductase + 2 mM NADPH), and liquid phase-gel phase ratio (percent liquid phase) was assessed by compaction assay. Exposure to low Trx concentrations (1 microM) caused significant increases in the percentage of liquid phase of sputum. Maximal increases in percent liquid phase occurred with 30 microM Trx. Additional measurements revealed that sputum liquefaction by the Trx reducing system is dependent on NADPH concentration. The relative potency of the Trx reducing system also was compared with other disulfide-reducing agents. In contrast with Trx, glutathione and N-acetylcysteine were ineffective in liquefying sputum when used at concentrations <1 mM. Sputum viscoelasticity, measured by magnetic microrheometry, also was diminished significantly following 20-min treatment with 3, 10, or 30 microM Trx. Similarly, this reduction in viscoelasticty also was dependent on NADPH concentration. Further investigation has indicated that Trx treatment increases the solubility of high-molecular-weight glycoproteins and causes redistribution of extracellular DNA into the liquid phase of sputum. Recognizing that mucins are the major gel-forming glycoproteins in mucus, we suggest that Trx alters sputum rheology by enzymatic reduction of glycoprotein polymers present in sputum. 相似文献
7.
The efficacy of a vacuuming device to reduce Lygus lineolaris (Palisot de Beauvois) populations was evaluated over 3 yr in a day-neutral strawberry field. Immediately after treatments, a significant reduction of population estimates (by tapping of flower clusters) was observed for adults (75% of the time) and nymphs (50% of the time). Under the same conditions, control (i.e., vacuum turbine off) treatments significantly reduced adult population estimates 25% of the time. Lygus lineolaris tapping samples taken from strawberry plants adjacent to the treated zone did not show significant variations over sampling time, suggesting that no escape behavior occurred. This was supported by adult catches on sticky traps located in zones adjacent to the treated one. Our results suggest that vacuuming had inconsistent effect on tarnished plant bug populations and that L. lineolaris mobility plays a marginal role in the use of this control method. 相似文献
8.
Rancourt RC Keng PC Helt CE O'Reilly MA 《American journal of physiology. Lung cellular and molecular physiology》2001,280(4):L617-L626
Previous studies have shown that hyperoxia inhibits proliferation and increases the expression of the tumor suppressor p53 and its downstream target, the cyclin-dependent kinase inhibitor p21(CIP1/WAF1), which inhibits proliferation in the G1 phase of the cell cycle. To determine whether growth arrest was mediated through activation of the p21-dependent G1 checkpoint, the kinetics of cell cycle movement during exposure to 95% O2 were assessed in the Mv1Lu and A549 pulmonary adenocarcinoma cell lines. Cell counts, 5-bromo-2'-deoxyuridine incorporation, and cell cycle analyses revealed that growth arrest of both cell lines occurred in S phase, with A549 cells also showing evidence of a G1 arrest. Hyperoxia increased p21 in A549 but not in Mv1Lu cells, consistent with the activation of the p21-dependent G1 checkpoint. The ability of p21 to exert the G1 arrest was confirmed by showing that hyperoxia inhibited proliferation of HCT 116 colon carcinoma cells predominantly in G1, whereas an isogenic line lacking p21 arrested in S phase. The cell cycle arrest in S phase appears to be a p21-independent process caused by a gradual reduction in the rate of DNA strand elongation. Our data reveal that hyperoxia inhibits proliferation in G1 and S phase and demonstrate that p53 and p21 retain their ability to affect G1 checkpoint control during exposure to elevated O2 levels. 相似文献
9.
10.
Everitt R Minnema SE Wride MA Koster CS Hance JE Mansergh FC Rancourt DE 《Bioinformatics (Oxford, England)》2002,18(12):1692-1693
The Rancourt EST Database (RED) is a web-based system for the analysis, management, and dissemination of expressed sequence tags (ESTs). RED represents a flexible template DNA sequence database that can be easily manipulated to suit the needs of other laboratories undertaking mid-size sequencing projects. 相似文献