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1.
Goats and some sheep synthesize a juvenile hemoglobin, Hb C (alpha 2 beta
C2), at birth and produce this hemoglobin exclusively during severe anemia.
Sheep that synthesize this juvenile hemoglobin are of the A haplotype.
Other sheep, belonging to a separate group, the B haplotype, do not
synthesize hemoglobin C and during anemia continue to produce their adult
hemoglobin. To understand the basis for this difference we have determined
the structural organization of the beta- globin locus of B-type sheep by
constructing and isolating overlapping genomic clones. These clones have
allowed us to establish the linkage map 5' epsilon I-epsilon II-psi beta
I-beta B-epsilon III-epsilon IV- psi beta II-beta F3' in this haplotype.
Thus, B sheep lack four genes, including the BC gene, and have only eight
genes, compared with the 12 found in the goat globin locus. The goat
beta-globin locus is as follows: 5' epsilon I-epsilon II-psi beta X-beta
C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta
Y-beta F3'. Southern blot analysis of A-type sheep reveals that these
animals have a beta- globin locus similar to that of goat, i.e., 12 globin
genes. Thus, the beta-globin locus of B-haplotype sheep resembles that of
cows and may have retained the duplicated locus of the ancestor of cows and
sheep. Alternatively, the B-sheep locus arrangement may be the result of a
deletion of a four-gene set from the triplicated locus.
相似文献
2.
3.
Recent advances in molecular mutagenesis reveal that two of the mechanisms which contribute to mutagen-induced point mutations, the frequency of induced DNA damage and the repair rate of this damage, vary considerably along the genome. At a grosser level of genomic resolution, cytogeneticists now distinguish several classes of chromosome bands along human chromosomes. The hot spots for X-ray induced breaks (chromosome mutations) occur in certain band classes, while the hot spots for mitomycin C-induced exchanges or melphalan-induced breaks occur in other band classes. Knowledge of these mutation patterns is modifying our concepts of genome evolution. 相似文献
4.
J Filipski B Marczyński L Sadzińska G Chalupka M Chorazy 《Biochimica et biophysica acta》1977,478(1):33-43
The mechanism of the biological activity of the 1-nitro and 2-nitro aminoacridine derivatives containing the dimethylaminopropyl side chain was studied. RNA synthesis in the isolated rat liver nuclei was only slightly influenced by both compounds. They do not differ in their ability to form an intercalative complex with DNA. Only the 1-nitro derivative exhibited strong inhibitory effect on RNA biosynthesis and caused distinct ultrastructural changes (nucleolar segregation, chromatine margination etc.) in a living cell. The 1-nitro derivative binds covalently to DNA in vivo resulting in crosslink formation. It is concluded that the biological activity of 1-nitro acridine derivatives depends more on their crosslinking activity than on their ability to intercalate into DNA. 相似文献
5.
Plasmodium cynomolgi: immunization of a rhesus monkey with exoerythrocytic stages cultured in autologous hepatocytes 总被引:1,自引:0,他引:1
P Millet W E Collins C T Atkinson G H Campbell J R Broderson B G Brown V Filipski M Aikawa P Nguyen-Dinh 《Experimental parasitology》1991,72(1):91-98
To investigate the immune response to exoerythrocytic stages of malaria parasites, a rhesus monkey was immunized with autologous primary hepatocyte cultures infected with 7-day-old liver stage parasites of Plasmodium cynomolgi. A primary antibody response against EE stage antigens was obtained, and boosted after injection of homologous viable sporozoites. Antibodies directed against sporozoites and blood stages were also detected. The polyvalent immune response observed demonstrates the antigenicity of the liver stages and suggests their involvement in the general immune response against malaria. 相似文献
6.
Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2α and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action
and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function. 相似文献
7.
Competitive inhibition of nicking--closing enzymes may explain some biological effects of DNA intercalators 总被引:1,自引:0,他引:1
J Filipski 《FEBS letters》1983,159(1-2):6-12
Intercalating agents cause varied and multiple biological effects. These include the inhibition of RNA and DNA synthesis, frameshift mutations and protein-associated DNA breaks. However, some non-intercalating analogs of intercalating compounds behave similarly. The model of DNA intercalation does not adequately explain all these biological effects. It is suggested here that intercalators and similar compounds may competitively inhibit the closing reaction of some nicking--closing enzymes. Hypothetical mechanisms built on this suggestion are presented for the formation of protein associated DNA breaks, frameshift mutation, inhibition of macromolecular synthesis, and recombination. 相似文献
8.
Two silicone coatings have been evaluated for barnacle adhesion. One coating is an unfilled hydrosilation cured polydimethylsiloxane (PDMS) network, while the other is a room temperature vulcanized (RTV), filled, ethoxysiloxane cured PDMS elastomer, RTV11?. The adhesion strength of one species of barnacle, Balanus eburneus, to the hydrosilation coatings is in the range of 0.37–0.60 kg cm‐2 while the corresponding range for RTV11 is 0.64–0.90 kg cm‐2. The easier release of B. eburneus from the hydrosilation cured network compared to RTV11 is discussed in relationship to differences in bulk and surface properties. Preliminary results suggest bulk modulus may be the most important parameter in determining barnacle adhesion strength. In light or mechanical property analysis, a re‐evaluation of surface properties and chemical stability is presented. 相似文献
9.
Benjamin D. Stevens John Litchfield Jeffrey A. Pfefferkorn Karen Atkinson Christian Perreault Paul Amor Kevin Bahnck Martin A. Berliner Jessica Calloway Anthony Carlo David R. Derksen Kevin J. Filipski Mike Gumkowski Charanjeet Jassal Margit MacDougall Brendan Murphy Paul Nkansah John Pettersen Yan Zhang 《Bioorganic & medicinal chemistry letters》2013,23(24):6588-6592
Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. 相似文献
10.
Recent localization of cohesin association regions along the yeast chromatin fibre suggests that compositional variability of DNA in yeast is related to the function and organization of the chromosomal loops. The bases of the loops, where the chromatin fibre is attached to the chromosomal axis, are AT-rich, bind cohesin, and are flanked by genes transcribed convergently. The hotspots of meiotic recombination are mainly found in the GC-rich parts of the loops, ‘external’ with respect to the chromosomal axis, frequently in the vicinity of the promoters of divergently transcribed genes. There are two possible reasons why the regions of the hotspots of recombination were enriched in GC content during evolution. One is a biased repair of recombination intermediates, and the second is a selective advantage due to an increased chromatin accessibility, which may have the carriers of GC-enriched alleles over the carriers of AT-rich alleles. 相似文献