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51.
Kunihiko Hinohara Toshiaki Nakajima Michio Yasunami Shigeru Houda Taishi Sasaoka Ken Yamamoto Bok-Soo Lee Hiroki Shibata Yumiko Tanaka-Takahashi Megumi Takahashi Takuro Arimura Akinori Sato Taeko Naruse Jimin Ban Hidetoshi Inoko Yoshiji Yamada Motoji Sawabe Jeong-Euy Park Toru Izumi Akinori Kimura 《Human genetics》2009,126(4):539-547
Coronary artery disease (CAD) is based on the atherosclerosis of coronary artery and may manifest with myocardial infarction or angina pectoris. Although it is widely accepted that genetic factors are linked to CAD and several disease-related genes have been reported, only a few could be replicated suggesting that there might be some other CAD-related genes. To identify novel susceptibility loci for CAD, we used microsatellite markers in the screening and found six different candidate CAD loci. Subsequent single nucleotide polymorphism (SNP) association studies revealed an association between CAD and megakaryoblastic leukemia factor-1 gene (MKL1). The association with a promoter SNP of MKL1, ?184C > T, was found in a Japanese population and the association was replicated in another Japanese population and a Korean population. Functional analysis of the MKL1 promoter SNP suggested that the higher MKL1 expression was associated with CAD. These findings suggest that MKL1 is involved in the pathogenesis of CAD. 相似文献
52.
Taishi Sugawara Keisuke Ito Mitsunori Shiroishi Hidetsugu Asada Tatsuro Shimamura Norimichi Nomura Keiko Abe Takuya Kobayashi 《Biochemical and biophysical research communications》2009,382(4):704-710
Human TAS2 receptors (hTAS2Rs) perceive bitter tastants, but few studies have explored the structure-function relationships of these receptors. In this paper, we report our trials on the large-scale preparations of hTAS2Rs for structural analysis. Twenty-five hTAS2Rs were expressed using a GFP-fusion yeast system in which the constructs and the culture conditions (e.g., the signal sequence, incubation time and temperature after induction) were optimized by measuring GFP fluorescence. After optimization, five hTAS2Rs (hTAS2R7, hTAS2R8, hTAS2R16, hTAS2R41, and hTAS2R48) were expressed at levels greater than 1 mg protein/L of culture, which is a preferable level for purification and crystallization. Among these five bitter taste receptors, hTAS2R41 exhibited the highest detergent solubilization efficiency of 87.1% in n-dodecyl-β-d-maltopyranoside (DDM)/cholesteryl hemisuccinate (CHS). Fluorescence size-exclusion chromatography showed that hTAS2R41 exhibited monodispersity in DDM/CHS without aggregates, suggesting that hTAS2R41 is a good target for future crystallization trials. 相似文献
53.
Taishi Hashiguchi Shuji Mizumoto Shuhei Yamada Kazuyuki Sugahara 《Glycoconjugate journal》2010,27(1):49-60
The amniotic membrane (AM) is the innermost layer of fetal membranes and possesses various biological activities. Although
the mechanism underlying these biological activities remains unclear, unique components seem to be involved. AM contains various
extracellular matrix components such as type I collagen, laminin, fibronectin, hyaluronan, and proteoglycans bearing chondroitin
sulfate/dermatan sulfate (CS/DS) glycosaminoglycan side chains. Since CS/DS have been implicated in various biological processes,
we hypothesized that CS/DS in AM may play a major role in the biological activities of AM. Therefore, the structure and bioactivity
of the CS/DS chains from porcine fetal membranes (FM-CS/DS) were investigated. A compositional analysis using various chondroitinases
revealed that the characteristic DS domain comprised of iduronic acid-containing disaccharide units is embedded in FM-CS/DS,
along with predominant disaccharide units, GlcA-GalNAc, GlcA-GalNAc(4-O-sulfate), and GlcA-GalNAc(6-O-sulfate), where GlcA and GalNAc represent D-glucuronic acid and N-acetyl-D-galactosamine, respectively. The average molecular mass of FM-CS/DS chains was unusually large and estimated to
be 250 – 300 kDa. The FM-CS/DS chains showed neurite outgrowth-promoting activity, which was eliminated by digestion with
chondroitinase ABC of the CS/DS chains. This activity was suppressed by antibodies against growth factors including pleiotrophin,
midkine, and fibroblast growth factor-2, suggesting the involvement of these growth factors in the neurite outgrowth-promoting
activity. The binding of these growth factors to FM-CS/DS was also demonstrated by surface plasmon resonance spectroscopy. 相似文献
54.
Yamamoto E Nakamura T Kataoka K Tokutomi Y Dong YF Fukuda M Nako H Yasuda O Ogawa H Kim-Mitsuyama S 《Biochemical and biophysical research communications》2010,403(3-4):258-263
The effect of calcium channel blockers (CCBs) on type 2 diabetes is still unclear. The present study was undertaken to examine the efficacy of nifedipine, a dihydropyridine CCB, on obesity, glucose intolerance and vascular endothelial dysfunction in db/db mice (a mouse model of obesity and type 2 diabetes). db/db mice, fed high-fat diet (HFD) were treated with vehicle, nifedipine (10 mg kg(-1) day(-1)) or hydralazine (5 mg kg(-1) day(-1)) for 4 weeks, and the protective effects were compared. Although nifedipine and hydralazine exerted similar blood pressure lowering in db/db mice, neither affected body weight, fat weight, and glucose intolerance of db/db mice. However, nifedipine, but not hydralazine, significantly improved vascular endothelial function in db/db mice, being accompanied by more attenuation of vascular superoxide by nifedipine than hydralazine. These protective effects of nifedipine were attributed to the attenuation of eNOS uncoupling as shown by the prevention of vascular endothelial nitric oxide synthase (eNOS) dimer disruption, and the prevention of dihydrofolate reductase (DHFR) downregulation, the key enzyme responsible for eNOS uncoupling. Moreover, nifedipine, but not hydralazine, significantly prevented the decreases in phosphorylation of vascular akt and eNOS in db/db mice. Our work provided the first evidence that nifedipine prevents vascular endothelial dysfunction, through the inhibition of eNOS uncoupling and the enhancement of eNOS phosphorylation, independently of blood pressure-lowering effect. We propose that nifedipine may be a promising therapeutic agent for cardiovascular complications in type 2 diabetes. 相似文献
55.
Tomoharu Tsukada Osamu Kanno Takahiro Yamane Jun Tanaka Taishi Yoshida Akira Okuno Takeshi Shiiki Mizuki Takahashi Takahide Nishi 《Bioorganic & medicinal chemistry》2010,18(14):5346-5351
With the aim of exploring the effect of tricyclic-based FBPase inhibitors in cells and in vivo, a series of prodrugs of tricyclic phosphonates was designed and synthesized. Introducing prodrug moieties into tricyclic-based phosphonates led to the discovery of prodrug 15c, which strongly inhibited glucose production in monkey hepatocytes. Furthermore, prodrug 15c lowered blood glucose levels in fasted cynomolgus monkeys. 相似文献
56.
Ren Yuan Taishi Nagao Peter D Paré James C Hogg Don D Sin Mark W Elliott Leanna Loy Li Xing Steven E Kalloger John C English John R Mayo Harvey O Coxson 《Respiratory research》2010,11(1):153
Objective
To refine the CT prediction of emphysema by comparing histology and CT for specific regions of lung. To incorporate both regional lung density measured by CT and cluster analysis of low attenuation areas for comparison with histological measurement of surface area per unit lung volume.Methods
The histological surface area per unit lung volume was estimated for 140 samples taken from resected lung specimens of fourteen subjects. The region of the lung sampled for histology was located on the pre-operative CT scan; the regional CT median lung density and emphysematous lesion size were calculated using the X-ray attenuation values and a low attenuation cluster analysis. Linear mixed models were used to examine the relationships between histological surface area per unit lung volume and CT measures.Results
The median CT lung density, low attenuation cluster analysis, and the combination of both were important predictors of surface area per unit lung volume measured by histology (p < 0.0001). Akaike''s information criterion showed the model incorporating both parameters provided the most accurate prediction of emphysema.Conclusion
Combining CT measures of lung density and emphysematous lesion size provides a more accurate estimate of lung surface area per unit lung volume than either measure alone. 相似文献57.
Ana Maria S. Sim?o Manisha C. Yadav Sonoko Narisawa Mayte Bolean Joao Martins Pizauro Marc F. Hoylaerts Pietro Ciancaglini José Luis Millán 《The Journal of biological chemistry》2010,285(10):7598-7609
We have established a proteoliposome system as an osteoblast-derived matrix vesicle (MV) biomimetic to facilitate the study of the interplay of tissue-nonspecific alkaline phosphatase (TNAP) and NPP1 (nucleotide pyrophosphatase/phosphodiesterase-1) during catalysis of biomineralization substrates. First, we studied the incorporation of TNAP into liposomes of various lipid compositions (i.e. in pure dipalmitoyl phosphatidylcholine (DPPC), DPPC/dipalmitoyl phosphatidylserine (9:1 and 8:2), and DPPC/dioctadecyl-dimethylammonium bromide (9:1 and 8:2) mixtures. TNAP reconstitution proved virtually complete in DPPC liposomes. Next, proteoliposomes containing either recombinant TNAP, recombinant NPP1, or both together were reconstituted in DPPC, and the hydrolysis of ATP, ADP, AMP, pyridoxal-5′-phosphate (PLP), p-nitrophenyl phosphate, p-nitrophenylthymidine 5′-monophosphate, and PPi by these proteoliposomes was studied at physiological pH. p-Nitrophenylthymidine 5′-monophosphate and PLP were exclusively hydrolyzed by NPP1-containing and TNAP-containing proteoliposomes, respectively. In contrast, ATP, ADP, AMP, PLP, p-nitrophenyl phosphate, and PPi were hydrolyzed by TNAP-, NPP1-, and TNAP plus NPP1-containing proteoliposomes. NPP1 plus TNAP additively hydrolyzed ATP, but TNAP appeared more active in AMP formation than NPP1. Hydrolysis of PPi by TNAP-, and TNAP plus NPP1-containing proteoliposomes occurred with catalytic efficiencies and mild cooperativity, effects comparable with those manifested by murine osteoblast-derived MVs. The reconstitution of TNAP and NPP1 into proteoliposome membranes generates a phospholipid microenvironment that allows the kinetic study of phosphosubstrate catabolism in a manner that recapitulates the native MV microenvironment. 相似文献
58.
The phytohormone abscisic acid (ABA), an important bioactive compound in plants, is implicated in several essential processes such as development and the abiotic stress response. Many components have been reported to have roles in these processes. Although 2C-type protein phosphatases (PP2C) and SNF1-related protein kinases2 (SnRK2) family are known to be important signal mediators, the molecular mechanisms by which these components regulate the ABA signaling pathway have not been elucidated. Recent identification of soluble ABA receptors, PYR/PYL/RCAR, has provided a major breakthrough in understanding the signaling mechanisms of ABA and revealed the importance of PP2Cs. In addition, the physical, biochemical and physiological connections between PP2C and SnRK2 have been clearly demonstrated. Taken together, the molecular basis of the major ABA signaling pathway has been established, from perception to gene expression. In this addendum, we discuss this emerging ABA signaling pathway, which has a conventional protein phosphorylation/dephosphorylation regulatory circuit and consider its physiological and functional relevance.Key words: ABA receptor, abscisic acid, PP2C, signal transduction, SnRK2, plant hormone, phosphoarylation 相似文献
59.
Pilson Choi Yoshiro Mano Atsuko Ishikawa Masashi Odashima Taishi Umezawa Tatsuhito Fujimura Yoshihito Takahata Takao Komatsuda 《Plant biotechnology reports》2010,4(1):23-27
Quantitative trait loci (QTLs) controlling ability of somatic embryogenesis were identified in soybean. A frame map with 204-point
markers was developed using an RI population consisting of 117 F11 lines derived from a cross between cultivar ‘Keburi’ and a weedy soybean ‘Masshokutou Kou 502’. The parents differed greatly
in their abilities of somatic embryogenesis using immature cotyledons as explants. The ability of somatic embryogenesis was
evaluated in five different experiments: the F11 (evaluated in 1998) and F15 (2002) generations cultured on basal media supplemented with 40 mg l−1 2,4-D (2,4-D1998 and 2,4-D2002), F14 (2001) generation on medium with 40 mg l−1 2,4-D and high sucrose concentration [2,4-D2001 (30 g l−1 sucrose)], and the F11 (1998) and F12 (1999) generations on medium with 10 mg l−1 NAA (NAA1998 and NAA1999). The RILs showed wide and continuous variations in each of the five experiments. In the composite
interval mapping analysis, 2 QTLs were found in group 8 (D1b + W, LOD = 5.42, r
2 = 37.5) in the experiment of 2,4-D1998 and in group 6 (C2, LOD = 6.03, r
2 = 26.0) in the experiment of 2,4-D2001 (high concentration sucrose). In both QTLs, alleles of ‘Masshokutou Kou 502’ with
high ability of somatic embryogenesis contributed to the QTLs. For the other three experiments, no QTL was detected in the
criteria of LOD >3.0, suggesting the presence of minor genes. 相似文献
60.
Alonso A Narisawa S Bogetz J Tautz L Hadzic R Huynh H Williams S Gjörloff-Wingren A Bremer MC Holsinger LJ Millan JL Mustelin T 《The Journal of biological chemistry》2004,279(31):32586-32591
The human DUSP15 gene encodes an uncharacterized 235-amino acid member of the subfamily of small dual specificity protein phosphatases related to the Vaccinia virus VH1 phosphatase. Similar to VHR-related MKPX (VHX) (DUSP22), the predicted protein has an N-terminal myristoylation recognition sequence, and we show here that both are indeed modified by the attachment of a myristate to Gly-2. In recognition of this relatedness to VHX, we refer to the DUSP15-encoded protein as VH1-related member Y (VHY). We report that VHY is expressed at high levels in the testis and barely detectable levels in the brain, spinal cord, and thyroid. A VHY-specific antiserum detected a protein with an apparent molecular mass of 26 kDa, and histochemical analysis showed that VHY was readily detectable in pachytene spermatocytes (midstage of meiotic division I) and round spermatids and weakly in Leydig cells (somatic cells outside of the seminiferous tubules). When expressed in 293T or NIH-3T3 cells, VHY was concentrated at the plasma membrane with some staining of vesicular structures in the Golgi region. Mutation of the myristoylation site Gly-2 abrogated membrane location. Finally, we demonstrate that VHY is an active phosphatase in vitro. We conclude that VHY is a new member of a subgroup of myristoylated VH1-like small dual specificity phosphatases. 相似文献