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排序方式: 共有141条查询结果,搜索用时 31 毫秒
31.
Bourret G Brodeur MR Luangrath V Lapointe J Falstrault L Brissette L 《The international journal of biochemistry & cell biology》2006,38(7):1160-1170
In blood circulation, low density lipoproteins (LDL) can undergo modification, such as oxidation, and become key factors in the development of atherosclerosis. Although the liver is the major organ involved in the elimination of oxidized LDL (oxLDL), the identity of the receptor(s) involved remains to be defined. Our work aims to clarify the role of the scavenger receptor class B type I (SR-BI) in the hepatic metabolism of mildly and standardly oxLDL as well as the relative contribution of parenchymal (hepatocytes) and nonparenchymal liver cells with a special emphasis on CE-selective uptake. The association of native LDL and mildly or standardly oxLDL labeled either in proteins or in cholesteryl esters (CE) was measured on primary cultures of mouse hepatocytes from normal and SR-BI knock-out (KO) mice. These in vitro assays demonstrated that hepatocytes are able to mediate CE-selective uptake from both LDL and oxLDL and that SR-BI KO hepatocytes have a 60% reduced ability to selectively take CE from LDL but not towards mildly or standardly oxLDL. When lipoproteins were injected in the mouse inferior vena cava, parenchymal and nonparenchymal liver cells accumulated more CE than proteins from native, mildly and standardly oxLDL, indicating that selective uptake of CE from these lipoproteins occurs in vivo in these two cell types. The parenchymal cells contribute near 90% of the LDL-CE selective uptake and SR-BI for 60% of this pathway. Nonparenchymal cells capture mainly standardly oxLDL while parenchymal and nonparenchymal cells equally take up mildly oxLDL. An 82% reduction of standardly oxLDL-CE selective uptake by the nonparenchymal cells of SR-BI KO mice allowed emphasizing the contribution of SR-BI in hepatic metabolism of standardly oxLDL. However, SR-BI is not responsible for mildly oxLDL metabolism. Thus, SR-BI is involved in LDL- and standardly oxLDL-CE selective uptake in parenchymal and nonparenchymal cells, respectively. 相似文献
32.
Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation 总被引:13,自引:0,他引:13
Sharov AA Weiner L Sharova TY Siebenhaar F Atoyan R Reginato AM McNamara CA Funa K Gilchrest BA Brissette JL Botchkarev VA 《The EMBO journal》2003,22(12):2992-3003
Contact of developing sensory organs with the external environment is established via the formation of openings in the skin. During eye development, eyelids first grow, fuse and finally reopen, thus providing access for visual information to the retina. Here, we show that eyelid opening is strongly inhibited in transgenic mice overexpressing the bone morphogenetic protein (BMP) antagonist noggin from the keratin 5 (K5) promoter in the epidermis. In wild-type mice, enhanced expression of the kinase-inactive form of BMPR-IB mediated by an adenovirus vector also inhibits eyelid opening. Noggin overexpression leads to reduction of apoptosis and retardation of cell differentiation in the eyelid epithelium, which is associated with downregulation of expression of the apoptotic receptors (Fas, p55 kDa TNFR), Id3 protein and keratinocyte differentiation markers (loricrin, involucrin). BMP-4, but not EGF or TGF-alpha, accelerates opening of the eyelid explants isolated from K5-Noggin transgenic mice when cultured ex vivo. These data suggest that the BMP signaling pathway plays an important role in regulation of genetic programs of eyelid opening and skin remodeling during the final steps of eye morphogenesis. 相似文献
33.
Transmembrane signalling by a hybrid protein: communication from the domain of chemoreceptor Trg that recognizes sugar-binding proteins to the kinase/phosphatase domain of osmosensor EnvZ. 总被引:6,自引:1,他引:5 下载免费PDF全文
J W Baumgartner C Kim R E Brissette M Inouye C Park G L Hazelbauer 《Journal of bacteriology》1994,176(4):1157-1163
Chemoreceptor Trg and osmosensor EnvZ of Escherichia coli share a common transmembrane organization but have essentially unrelated primary structures. We created a hybrid gene coding for a protein in which Trg contributed its periplasmic and transmembrane domains as well as a short cytoplasmic segment and EnvZ contributed its cytoplasmic kinase/phosphatase domain. Trz1 transduced recognition of sugar-occupied, ribose-binding protein by its periplasmic domain into activation of its cytoplasmic kinase/phosphatase domain as assessed in vivo by using an ompC-lacZ fusion gene. Functional coupling of sugar-binding protein recognition to kinase/phosphatase activity indicates shared features of intramolecular signalling in the two parent proteins. In combination with previous documentation of transduction of aspartate recognition by an analogous fusion protein created from chemoreceptor Tar and EnvZ, the data indicate a common mechanism of transmembrane signal transduction by chemoreceptors and EnvZ. Signalling through the fusion proteins implies functional interaction between heterologous domains, but the minimal sequence identity among relevant segments of EnvZ, Tar, and Trg indicates that the link does not require extensive, specific interactions among side chains. The few positions of identity in those three sequences cluster in transmembrane segment 1 and the short chemoreceptor sequence in the cytoplasmic part of the hybrid proteins. These regions may be particularly important in physical and functional coupling. The specific cellular conditions necessary to observe ligand-dependent activation of Trz1 can be understood in the context of the importance of phosphatase control in EnvZ signalling and limitations on maximal receptor occupancy in binding protein-mediated recognition. 相似文献
34.
The genomes of homeothermic (warm-blooded) vertebrates are mosaic
interspersions of homogeneously GC-rich and GC-poor regions (isochores).
Evolution of genome compartmentalization and GC-rich isochores is
hypothesized to reflect either selective advantages of an elevated GC
content or chromosome location and mutational pressure associated with the
timing of DNA replication in germ cells. To address the present controversy
regarding the origins and maintenance of isochores in homeothermic
vertebrates, newly obtained as well as published nucleotide sequences of
the insulin and insulin-like growth factor (IGF) genes, members of a
well-characterized gene family believed to have evolved by repeated
duplication and divergence, were utilized to examine the evolution of base
composition in nonconstrained (flanking) and weakly constrained (introns
and fourfold degenerate sites) regions. A phylogeny derived from amino acid
sequences supports a common evolutionary history for the insulin/IGF family
genes. In cold- blooded vertebrates, insulin and the IGFs were similar in
base composition. In contrast, insulin and IGF-II demonstrate dramatic
increases in GC richness in mammals, but no such trend occurred in IGF- I.
Base composition of the coding portions of the insulin and IGF genes across
vertebrates correlated (r = 0.90) with that of the introns and flanking
regions. The GC content of homologous introns differed dramatically between
insulin/IGF-II and IGF-I genes in mammals but was similar to the GC level
of noncoding regions in neighboring genes. Our findings suggest that the
base composition of introns and flanking regions is determined by
chromosomal location and the mutational pressure of the isochore in which
the sequences are embedded. An elevated GC content at codon third positions
in the insulin and the IGF genes may reflect selective constraints on the
usage of synonymous codons.
相似文献
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38.
Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death 总被引:2,自引:0,他引:2
Calautti E Li J Saoncella S Brissette JL Goetinck PF 《The Journal of biological chemistry》2005,280(38):32856-32865
Signaling pathways regulating the differentiation program of epidermal cells overlap widely with those activated during apoptosis. How differentiating cells remain protected from premature death, however, is still poorly defined. We show here that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated at early stages of mouse keratinocyte differentiation both in culture and in the intact epidermis in vivo. Expression of active Akt in keratinocytes promotes growth arrest and differentiation, whereas pharmacological blockade of PI3K inhibits the expression of "late" differentiation markers and leads to death of cells that would otherwise differentiate. Mechanistically, the activation of the PI3K/Akt pathway in keratinocyte differentiation depends on the activity of the epidermal growth factor receptor and Src families of tyrosine kinases and the engagement of E-cadherin-mediated adhesion. During this process, PI3K associates increasingly with cadherin-catenin protein complexes bearing tyrosine phosphorylated YXXM motifs. Thus, the PI3K signaling pathway regulates the choice between epidermal cell differentiation and death at the cross-talk between tyrosine kinases and cadherin-associated catenins. 相似文献
39.
Nelson RT Boyd J Gladue RP Paradis T Thomas R Cunningham AC Lira P Brissette WH Hayes L Hames LM Neote KS McColl SR 《Genomics》2001,73(1):28-37
We describe the genomic organization of a recently identified CC chemokine, MIP3alpha/CCL20 (HGMW-approved symbol SCYA20). The MIP-3alpha/CCL20 gene was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISH analysis to 2q35-q36. Two distinct cDNAs were identified, encoding two forms of MIP-3alpha/CCL20, Ala MIP-3alpha/CCL20 and Ser MIP-3alpha/CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the boundary of intron 1 and exon 2 showed that use of alternative splice acceptor sites could give rise to Ala MIP-3alpha/CCL20 or Ser MIP-3alpha/CCL20. Both forms of MIP-3alpha/CCL20 were chemically synthesized and tested for biological activity. Both flu antigen plus IL-2-activated CD4(+) and CD8(+) T lymphoblasts and cord blood-derived dendritic cells responded to Ser and Ala MIP-3alpha/CCL20. T lymphocytes exposed only to IL-2 responded inconsistently, while no response was detected in naive T lymphocytes, monocytes, or neutrophils. The biological activity of Ser MIP-3alpha/CCL20 and Ala MIP-3alpha/CCL20 and the tissue-specific preference of different splice acceptor sites are not yet known. 相似文献
40.
Erik HFM van der Heijden Wouter Hoefsloot Hieronymus WH van Hees Olga CJ Schuurbiers 《Respiratory research》2015,16(1)