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排序方式: 共有167条查询结果,搜索用时 15 毫秒
1.
Chiara Pavanello Alice Ossoli Arianna Strazzella Patrizia Risè Fabrizio Veglia Marie Lhomme Paolo Parini Laura Calabresi 《Journal of lipid research》2022,63(7):100232
Mutations in the LCAT gene cause familial LCAT deficiency (Online Mendelian Inheritance in Man ID: #245900), a very rare metabolic disorder. LCAT is the only enzyme able to esterify cholesterol in plasma, whereas sterol O-acyltransferases 1 and 2 are the enzymes esterifying cellular cholesterol in cells. Despite the complete lack of LCAT activity, patients with familial LCAT deficiency exhibit circulating cholesteryl esters (CEs) in apoB-containing lipoproteins. To analyze the origin of these CEs, we investigated 24 carriers of LCAT deficiency in this observational study. We found that CE plasma levels were significantly reduced and highly variable among carriers of two mutant LCAT alleles (22.5 [4.0–37.8] mg/dl) and slightly reduced in heterozygotes (218 [153–234] mg/dl). FA distribution in CE (CEFA) was evaluated in whole plasma and VLDL in a subgroup of the enrolled subjects. We found enrichment of C16:0, C18:0, and C18:1 species and a depletion in C18:2 and C20:4 species in the plasma of carriers of two mutant LCAT alleles. No changes were observed in heterozygotes. Furthermore, plasma triglyceride-FA distribution was remarkably similar between carriers of LCAT deficiency and controls. CEFA distribution in VLDL essentially recapitulated that of plasma, being mainly enriched in C16:0 and C18:1, while depleted in C18:2 and C20:4. Finally, after fat loading, chylomicrons of carriers of two mutant LCAT alleles showed CEs containing mainly saturated FAs. This study of CEFA composition in a large cohort of carriers of LCAT deficiency shows that in the absence of LCAT-derived CEs, CEs present in apoB-containing lipoproteins are derived from hepatic and intestinal sterol O-acyltransferase 2. 相似文献
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Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
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E. Trévisiol E. Defrancq J. Lhomme A. Laayoun A. Hoang F. Besème 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):979-980
Abstract We report a novel strategy for Post-Amplification Labelling based upon coupling nucleotide incorporating an oxyamino function with a fluorophore bearing an aldehydic group. 相似文献
6.
Didier Boturyn Eric Defrancq Veacute; onique Ducros Catherine Fontaine Jean Lhomme 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):2069-2077
Abstract Reaction of abasic site-containing oligonucleotides with an oxyamino fluorescent label is described. The reaction represents an efficient method to functionalize oligonucleotides at preselected positions. 相似文献
7.
Loss of a base in DNA, i.e., creation of an abasic site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously, or under the action of radiations and alkylating agents, or enzymatically as an intermediate in the repair of modified or abnormal bases. The abasic site lesion is mutagenic or lethal if not repaired. From a chemical point of view,the abasic site is an alkali-labile residue that leads to strand breakage through beta- and delta- elimination. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of synthetic abasic duplexes. Several efficient synthetic methods have thus been developed to introduce the lesion (or a stable analogue) at defined position in the sequence. Physicochemical and spectroscopic examination of such duplexes, including calorimetry, melting temperature, high-field nmr and molecular modeling indicate that the lesion strongly destabilizes the duplex, although remaining in the canonical B-form with structural modifications strictly located at the site of the lesion. Probes have been developed to titrate the damage in DNA in vitro. Series of molecules have been devised to recognize specifically the abasic site, exhibiting a cleavage activity and mimicking the AP nucleases. Others have been prepared that bind strongly to the abasic site and show promise in potentiating the cytotoxic and antitumor activity of the clinically used nitrosourea (bis-chloroethylnitrosurea). 相似文献
8.
The abasic site is a common lesion in DNA that is also formed as an intermediate in the base excision repair of damaged bases. We have previously reported the adenine-acridine conjugate 1 that was designed to bind to the abasic site and interfere with the repair process. High-field NMR had shown that 1 forms specific complexes with a DNA duplex containing an apurinic abasic site model. We report here the dynamics of the interaction of the nitroxide-labeled analogue 3 of the conjugate 1 with the same apurinic oligonucleotide and with the parent unmodified duplex. Identical study of the labeled acridine subunit 5 used as a reference is also reported. In the presence of the apurinic duplex and depending on the concentrations and drug ratios, three species are observed: the radical "free in solution", the "intercalation" complex characterized by its similarity to that observed in the presence of the parent unmodified duplex, and the "abasic-site-specific" complex which is the sole species visible at low drug ratios. The experimental data reinforced by molecular modeling of the complex and theoretical calculation of correlation times suggest (i) the most immobilized form corresponds to that observed by NMR and (ii) complexation of the drug is little or not modified by the spin-label. We also show that the abasic site constitutes a binding site for the propylaminoacridine intercalator 5. 相似文献
9.
Background
In addition to known protein-coding genes, large amounts of apparently non-coding sequence are conserved between the human and mouse genomes. It seems reasonable to assume that these conserved regions are more likely to contain functional elements than less-conserved portions of the genome. 相似文献10.
Diversity-stability relationships in community ecology: re-examination of the portfolio effect 总被引:4,自引:0,他引:4
In plant communities, the portfolio effect, also called "statistical averaging effect", expresses the fact that stability in aggregate community properties such as biomass productivity generally rises with species diversity, simply because of the statistical averaging of the fluctuations in species' properties. This paper essentially upgrades the previous formulations of the portfolio effect, first developed by Doak and collaborators and then by Tilman. It uses a theoretical approach based on simple statistical relationships and some simplifying assumptions proposed by these authors. The new formulation presented extends and improves the previous relationships in the sense that it takes into account simultaneously a varying scaling power of the variance, the interaction effect between species, the heterogeneity in species productivity and interspecies correlated responses to the environment. It appears that the simple statistical averaging, as inferred from this formulation, does not necessarily lead to a positive correlation between species diversity and community stability. 相似文献