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排序方式: 共有908条查询结果,搜索用时 31 毫秒
61.
Aguado E Richelme S Nuñez-Cruz S Miazek A Mura AM Richelme M Guo XJ Sainty D He HT Malissen B Malissen M 《Science (New York, N.Y.)》2002,296(5575):2036-2040
The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (TH) cells that chronically produced type 2 cytokines in large amounts. This exaggerated TH2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of TH cells. 相似文献
62.
Klein RF Allard J Avnur Z Nikolcheva T Rotstein D Carlos AS Shea M Waters RV Belknap JK Peltz G Orwoll ES 《Science (New York, N.Y.)》2004,303(5655):229-232
The development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development. Pharmacologic inhibitors of this enzyme improved bone density and strength in two rodent models of osteoporosis. These results suggest that drugs targeting the 12/15-lipoxygenase pathway merit investigation as a therapy for osteoporosis. 相似文献
63.
RNA secondary structure repression of a muscle-specific exon in HeLa cell nuclear extracts 总被引:44,自引:0,他引:44
B Clouet d'Orval Y d'Aubenton Carafa P Sirand-Pugnet M Gallego E Brody J Marie 《Science (New York, N.Y.)》1991,252(5014):1823-1828
The chicken beta-tropomyosin pre-messenger RNA (pre-mRNA) is spliced in a tissue-specific manner to yield messenger RNA's (mRNA's) coding for different isoforms of this protein. Exons 6A and 6B are spliced in a mutually exclusive manner; exon 6B was included in skeletal muscle, whereas exon 6A was preferred in all other tissues. The distal portion of the intron upstream of exon 6B was shown to form stable double-stranded regions with part of the intron downstream of exon 6B and with sequences in exon 6B. This structure repressed splicing of exon 6B to exon 7 in a HeLa cell extract. Derepression of splicing occurred on disruption of this structure and repression followed when the structure was re-formed, even if the structure was formed between two different RNA molecules. Repression leads to inhibition of formation of spliceosomes. Disrupting either of the two double-stranded regions could lead to derepression, whereas re-forming the helices by suppressor mutations reestablished repression. These results support a simple model of tissue-specific splicing in this region of the pre-mRNA. 相似文献
64.
Pyle AM 《Science (New York, N.Y.)》2005,309(5740):1530-1531
The number of naturally occurring RNA enzymes has just been expanded by the discovery of a new branching ribozyme. But this ribozyme has unexpected relatives: group I introns. 相似文献
65.
66.
Fortunel NO Otu HH Ng HH Chen J Mu X Chevassut T Li X Joseph M Bailey C Hatzfeld JA Hatzfeld A Usta F Vega VB Long PM Libermann TA Lim B 《Science (New York, N.Y.)》2003,302(5644):393; author reply 393
67.
Walmsley MJ Ooi SK Reynolds LF Smith SH Ruf S Mathiot A Vanes L Williams DA Cancro MP Tybulewicz VL 《Science (New York, N.Y.)》2003,302(5644):459-462
The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance. 相似文献
68.
Lin EK Soles CL Goldfarb DL Trinque BC Burns SD Jones RL Lenhart JL Angelopoulos M Willson CG Satija SK Wu WL 《Science (New York, N.Y.)》2002,297(5580):372-375
The continuing drive by the semiconductor industry to fabricate smaller structures using photolithography will soon require dimensional control at length scales comparable to the size of the polymeric molecules in the materials used to pattern them. The current technology, chemically amplified photoresists, uses a complex reaction-diffusion process to delineate patterned areas with high spatial resolution. However, nanometer-level control of this critical process is limited by the lack of direct measurements of the reaction front. We demonstrate the use of x-ray and neutron reflectometry as a general method to measure the spatial evolution of the reaction-diffusion process with nanometer resolution. Measuring compositional profiles, provided by deuterium-labeled reactant groups for neutron scattering contrast, we show that the reaction front within the material is broad rather than sharply defined and the compositional profile is altered during development. Measuring the density profile, we directly correlate the developed film structure with that of the reaction front. 相似文献
69.
70.
Cakir-Kiefer C Le Roux Y Balandras F Trabalon M Dary A Laurent F Gaillard JL Miclo L 《Journal of agricultural and food chemistry》2011,59(9):4464-4472
α-Casozepine is a peptide, corresponding to the sequence 91-100 of the bovine α(s1)-casein, displaying anxiolytic activity in the rat. The α(s1)-casein tryptic hydrolysate containing this peptide decreases stress effects after oral administration in various species including man. Therefore, the stability of this peptide toward gastric and pancreatic proteases has been assessed by using pepsin, chymotrypsin/trypsin, Corolase PP, pepsin followed by chymotrypsin/trypsin or pepsin followed by Corolase PP. α-Casozepine was slowly degraded by chymotrypsin, much more sensitive to pepsin and Corolase PP but not completely destroyed after 4 h kinetics. The bonds in the region 91 to 95 of the α-casozepine were totally resistant to hydrolysis by all studied proteases. Surprisingly, a fragment, corresponding to the sequence 91-97 and found in all the hydrolysis media in significant amount, possessed an anxiolytic activity in three behavioral tests measuring this parameter. This peptide could participate in the in vivo activity of α-casozepine. 相似文献