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61.
Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of alpha-dystroglycan
Xiong H Kobayashi K Tachikawa M Manya H Takeda S Chiyonobu T Fujikake N Wang F Nishimoto A Morris GE Nagai Y Kanagawa M Endo T Toda T 《Biochemical and biophysical research communications》2006,350(4):935-941
The recent identification of mutations in genes encoding demonstrated or putative glycosyltransferases has revealed a novel mechanism for congenital muscular dystrophy. Hypoglycosylated alpha-dystroglycan (alpha-DG) is commonly seen in Fukuyama-type congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), Walker-Warburg syndrome (WWS), and Large(myd) mice. POMGnT1 and POMTs, the gene products responsible for MEB and WWS, respectively, synthesize unique O-mannose sugar chains on alpha-DG. The function of fukutin, the gene product responsible for FCMD, remains undetermined. Here we show that fukutin co-localizes with POMGnT1 in the Golgi apparatus. Direct interaction between fukutin and POMGnT1 was confirmed by co-immunoprecipitation and two-hybrid analyses. The transmembrane region of fukutin mediates its localization to the Golgi and participates in the interaction with POMGnT1. Y371C, a missense mutation found in FCMD, retains fukutin in the ER and also redirects POMGnT1 to the ER. Finally, we demonstrate reduced POMGnT1 enzymatic activity in transgenic knock-in mice carrying the retrotransposal insertion in the fukutin gene, the prevalent mutation in FCMD. From these findings, we propose that fukutin forms a complex with POMGnT1 and may modulate its enzymatic activity. 相似文献
62.
63.
Ito E Tominaga A Waki H Miseki K Tomioka A Nakajima K Kakehi K Suzuki M Taniguchi N Suzuki A 《Neurochemical research》2012,37(6):1315-1324
The atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) is a quite convenient soft ionization for
biomolecules, keeping analytes atmospheric conditions instead of high vacuum conditions. In this study, an AP-MALDI ion source
has been coupled to a quadrupole ion trap time-of-flight (QIT-TOF) mass spectrometer, which is able to perform MSn analysis. We applied this system to the structural characterization of monosialogangliosides, GM1 (NeuAc) and GM2 (NeuAc),
disialogangliosides, GD2 (NeuAc, NeuAc), GD1a (NeuAc, NeuAc) and GD1b (NeuAc, NeuAc) and trisialoganglioside GT1a (NeuAc,
NeuAc, NeuAc). In this system, the negative ion mass spectra of MS, MS2 and MS3, a set of three mass spectra, were able to measure within 2 s per cycle. Thus, obtained results demonstrate that the negative
ion mode MS, MS2 and MS3 spectra provided sufficient information for the determination of molecular weights, oligosaccharide sequences and ceramide
structures, and indicate that the AP-MALDI-QIT-TOF mass spectrometry keeping analytes atmospheric conditions with MSn switching is quite useful and convenient for structural analyses of various types of sialic acid-containing GSLs, gangliosides. 相似文献
64.
Koyanagi A Sekine C Yagita H 《Biochemical and biophysical research communications》2012,418(4):799-805
Notch plays multiple roles in T cell development in the thymus and T cell differentiation in the periphery. In order to systematically examine the role of Notch in T cell biology, we determined the cell surface expression of all Notch receptors and ligands on various populations of T cells by using a panel of specific monoclonal antibodies we recently established. Notch1 and Notch3 were upregulated at double-negative (DN) 2-DN4 stages of immature thymocytes, then downregulated on mature single-positive thymocytes and peripheral T cells, but were rapidly upregulated again upon activation. Notch2 was consistently expressed on T cells while Notch4 was not. Jagged1 and Jagged2 were expressed at double-positive stage of immature T cells. Jagged2 was also inducible on mature T cells upon activation. In contrast, no Delta-like (Dll) 1 or Dll4 expression was observed on T cells. These comprehensive profiling of the expression of Notch receptors and ligands would be informative to fully understand the role of individual Notch receptors and ligands in T cell development and differentiation. 相似文献
65.
Hiroaki Matsubara Yasunobu Shibasaki Mitsuhiko Okigaki Yasukiyo Mori Hiroya Masaki Atsushi Kosaki Yoshiaki Tsutsumi Yoko Uchiyama Soichiro Fujiyama Atsuko Nose Osamu Iba Eriko Tateishi Takamasa Hasegawa Masatsugu Horiuchi Clara Nahmias Toshiji Iwasaka 《Biochemical and biophysical research communications》2012,417(4):1316-1317
66.
Naito AT Sumida T Nomura S Liu ML Higo T Nakagawa A Okada K Sakai T Hashimoto A Hara Y Shimizu I Zhu W Toko H Katada A Akazawa H Oka T Lee JK Minamino T Nagai T Walsh K Kikuchi A Matsumoto M Botto M Shiojima I Komuro I 《Cell》2012,149(6):1298-1313
Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice, but not in those of C1qa-deficient mice. C1q activates canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt coreceptor low-density lipoprotein receptor-related protein 6. Skeletal muscle regeneration in young mice is inhibited by exogenous C1q treatment, whereas aging-associated impairment of muscle regeneration is restored by C1s inhibition or C1qa gene disruption. Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging. 相似文献
67.
Orange petals of calendula (Calendula officinalis) accumulate red carotenoids with the cis-configuration at the C-5 or C-5' position (5-cis-carotenoids). We speculated that the orange-flowered calendula is a carotenoid isomerase (crtiso) loss-of-function mutant that impairs the cis-to-trans conversion of 5-cis-carotenoids. We compared the sequences and enzyme activities of CRTISO from orange- and yellow-flowered calendulas. Four types of CRTISO were expressed in calendula petals. The deduced amino acid sequence of one of these genes (CoCRTISO1) was different between orange- and yellow-flowered calendulas, whereas the sequences of the other three CRTISOs were identical between these plants. Analysis of the enzymatic activities of the CoCRTISO homologs showed that CoCRTISO1-Y, which was expressed in yellow petals, converted carotenoids from the cis-to-trans-configuration, whereas both CoCRTISO1-ORa and 1-ORb, which were expressed in orange petals, showed no activity with any of the cis-carotenoids we tested. Moreover, the CoCRTISO1 genotypes of the F2 progeny obtained by crossing orange and yellow lines linked closely to petal color. These data indicate that CoCRTISO1 is a key regulator of the accumulation of 5-cis-carotenoids in calendula petals. Site-directed mutagenesis showed that the deletion of Cys-His-His at positions 462-464 in CoCRTISO1-ORa and a Gly-to-Glu amino acid substitution at position 450 in CoCRTISO1-ORb abolished enzyme activity completely, indicating that these amino acid residues are important for the enzymatic activity of CRTISO. 相似文献
68.
Ishijima M Suzuki N Hozumi K Matsunobu T Kosaki K Kaneko H Hassell JR Arikawa-Hirasawa E Yamada Y 《Matrix biology》2012,31(4):234-245
Perlecan (Hspg2) is a heparan sulfate proteoglycan expressed in basement membranes and cartilage. Perlecan deficiency (Hspg2(-/-)) in mice and humans causes lethal chondrodysplasia, which indicates that perlecan is essential for cartilage development. However, the function of perlecan in endochondral ossification is not clear. Here, we report the critical role of perlecan in VEGF signaling and angiogenesis in growth plate formation. The Hspg2(-/-) growth plate was significantly wider but shorter due to severely impaired endochondral bone formation. Hypertrophic chondrocytes were differentiated in Hspg2(-/-) growth plates; however, removal of the hypertrophic matrix and calcified cartilage was inhibited. Although the expression of MMP-13, CTGF, and VEGFA was significantly upregulated in Hspg2(-/-) growth plates, vascular invasion into the hypertrophic zone was impaired, which resulted in an almost complete lack of bone marrow and trabecular bone. We demonstrated that cartilage perlecan promoted activation of VEGF/VEGFR by binding to the VEGFR of endothelial cells. Expression of the perlecan transgene specific to the cartilage of Hspg2(-/-) mice rescued their perinatal lethality and growth plate abnormalities, and vascularization into the growth plate was restored, indicating that perlecan in the growth plate, not in endothelial cells, is critical in this process. These results suggest that perlecan in cartilage is required for activating VEGFR signaling of endothelial cells for vascular invasion and for osteoblast migration into the growth plate. Thus, perlecan in cartilage plays a critical role in endochondral bone formation by promoting angiogenesis essential for cartilage matrix remodeling and subsequent endochondral bone formation. 相似文献
69.
Nagata S Tomoeda M Kubo C Yoshizawa H Yuki M Kitamura M Takenaka A Uehara H Katayama K Nakanishi K Takahashi H Ohigashi H Ishikawa O Tomita Y 《Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]》2012,12(1):23-26
We present the first reported case of intraductal polypoid growth (IPG) variant of pancreatic acinar cell carcinoma (ACC) metastasizing to the intrahepatic bile duct. A 58-year-old Japanese woman had previously presented with obstructive jaundice and a 7.0 cm mass in the pancreatic head. She underwent biliary drainage for 2 months followed by pancreatectomy. Histological examination revealed a carcinoma with acinar pattern, immunohistochemically positive for trypsin, and acinar cell carcinoma was diagnosed. IPGs were prominent in the main pancreatic duct and its tributaries, extending into the intrapancreatic bile duct with tumor casts in the lumen. Imaging examinations 6 years later revealed a growing lesion within the intrahepatic bile duct. Needle biopsy examination suggested metastasis of ACC, and she underwent chemoradiation therapy and partial hepatectomy. Histological examination demonstrated ACC confined to the intrahepatic bile duct. The localization of metastasis and slow growth may indicate indolent biologic behavior of the IPG variant. 相似文献
70.