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11.
Kimihiko Shibata Atsuko Tarui Natsumi Todoroki Shinjiro Kawamoto Shouji Takahashi Yoshio Kera Ryo-hei Yamada 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2001,130(4)
The presence of N-methyl-
-aspartate (NMLA) was demonstrated in bivalves, Corbicula sandai and Tapes japonica. To our knowledge, this is the first report on the occurrence of NMLA in animal tissues. NMLA in bivalve tissues was identified according to the following findings; (a) its derivatives with (+)- and (−)- 1-(9-fluorenyl)ethyl chloroformate (FLEC) behaved identically with those of authentic NMLA, respectively, on high-performance liquid chromatography (HPLC), (b) its derivatives with (+)- and (−)- FLEC behaved identically with (−)- and (+)-FLEC derivatives of authentic N-methyl-
-aspartate (NMDA), respectively, on HPLC and (c) its behavior on thin-layer chromatography was the same as those of authentic NMLA. We also describe the distribution of NMDA, and
- and
-aspartate, to which N-methylaspartate enantiomers are structurally related. NMDA was more widely dirtributed than NMLA in bivalves. These bivalves containing NMLA showed lower
-aspartate contents and
/(
+
) ratios of aspartate, than the bivalves containing NMDA. 相似文献
12.
Let's think again about using mammalian temperature‐sensitive mutants to investigate functional molecules—The perspectives from the studies on three mutants showing chromosome instability 下载免费PDF全文
Kimihiko Sugaya 《Journal of cellular biochemistry》2018,119(9):7143-7150
This review evaluates the use of temperature‐sensitive (ts) mutants to investigate functional molecules in mammalian cells. A series of studies were performed in which mammalian cells expressing functional molecules were isolated from ts mutants using complementation by the introduction and expression of the responsible protein tagged with the green fluorescent protein. The results showed that chromosome instability and cell‐cycle arrest were caused by ts defects in the following three molecules: the largest subunit of RNA polymerase II, a protein involved in splicing, and ubiquitin‐activating enzyme. The cells expressing functional protein were then isolated by introducing the responsible gene tagged with the green fluorescent protein to complement the ts phenotype. These cells proved to be useful in analyzing the dynamics of RNA polymerase II in living cells. Analyses of the functional interaction between proteins involved in splicing were also useful in the investigation of ts mutants and their derivatives. In addition, these cells demonstrated the functional localization of ubiquitin‐activating enzyme in the nucleus. Mammalian ts mutants continue to show great potential to aid in understanding the functions of the essential molecules in cells. Therefore, it is highly important that studies on the identification and characterization of the genes responsible for the phenotype of a mutant are carried out. 相似文献
13.
A Double-Strand Break Repair Component Is Essential for S Phase Completion in Fission Yeast Cell Cycling 下载免费PDF全文
Kimihiko Suto Akihisa Nagata Hiroshi Murakami Hiroto Okayama 《Molecular biology of the cell》1999,10(10):3331-3343
Fission yeast rad22(+), a homologue of budding yeast RAD52, encodes a double-strand break repair component, which is dispensable for proliferation. We, however, have recently obtained a cell division cycle mutant with a temperature-sensitive allele of rad22(+), designated rad22-H6, which resulted from a point mutation in the conserved coding sequence leading to one amino acid alteration. We have subsequently isolated rad22(+) and its novel homologue rti1(+) as multicopy suppressors of this mutant. rti1(+) suppresses all the defects of cells lacking rad22(+). Mating type switch-inactive heterothallic cells lacking either rad22(+) or rti1(+) are viable, but those lacking both genes are inviable and arrest proliferation with a cell division cycle phenotype. At the nonpermissive temperature, a synchronous culture of rad22-H6 cells performs DNA synthesis without delay and arrests with chromosomes seemingly intact and replication completed and with a high level of tyrosine-phosphorylated Cdc2. However, rad22-H6 cells show a typical S phase arrest phenotype if combined with the rad1-1 checkpoint mutation. rad22(+) genetically interacts with rad11(+), which encodes the large subunit of replication protein A. Deletion of rad22(+)/rti1(+) or the presence of rad22-H6 mutation decreases the restriction temperature of rad11-A1 cells by 4-6 degrees C and leads to cell cycle arrest with chromosomes incompletely replicated. Thus, in fission yeast a double-strand break repair component is required for a certain step of chromosome replication unlinked to repair, partly via interacting with replication protein A. 相似文献
14.
Kiuchi M Adachi K Tomatsu A Chino M Takeda S Tanaka Y Maeda Y Sato N Mitsutomi N Sugahara K Chiba K 《Bioorganic & medicinal chemistry》2005,13(2):425-432
A practical asymmetric synthesis of both enantiomers of the immunosuppressive FTY720-phosphate (2) was accomplished, and the enantiomers were pharmacologically evaluated. Several lipases showed considerable activity and enantioselectivity for O-acylation of N-acetyl FTY720 (3) or N-benzyloxycarbonyl FTY720 (7) in combination with vinyl acetate or benzyl vinyl carbonate as the acyl donors. The synthesis using the lipase-catalyzed acylation as the key step produced the enantiomerically pure (>99.5% ee) enantiomers of 2 in multigram quantities. (S)-Isomer of 2 had more potent binding affinities to S1P(1,3,4,5) and inhibitory activity on lymphocyte migration toward S1P than (R)-2, suggesting that (S)-isomer of 2 is responsible for the immunosuppressive activity after administration of 1. Severe bradycardia was observed in anesthetized rats when (S)-2 was administered intravenously, while (R)-2 had no clear effect on heart rate up to 0.3 mg/kg. 相似文献
15.
Hirokazu Sakan Kimihiko Nakatani Osamu Asai Akihiro Imura Tomohiro Tanaka Shuhei Yoshimoto Noriyuki Iwamoto Norio Kurumatani Masayuki Iwano Yo-ichi Nabeshima Noboru Konishi Yoshihiko Saito 《PloS one》2014,9(1)
Renal α-Klotho (α-KL) plays a fundamental role as a co-receptor for fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). Disruption of FGF23-α-KL signaling is thought to be an early hallmark of chronic kidney disease (CKD) involving reduced renal α-KL expression and a reciprocal rise in serum FGF23. It remains unclear, however, whether the rise in FGF23 is related to the loss of renal α-KL. We evaluated α-KL expression in renal biopsy samples and measured levels of several parameters of mineral metabolism, as well as soluble α-KL (sKL), in serum and urinary samples from CKD patients (n = 236). We found that although renal α-KL levels were significantly reduced and serum FGF23 levels were significantly elevated in early and intermediate CKD, serum phosphate levels remained within the normal range. Multiple regression analysis showed that the increases in FGF23 were significantly associated with reduced renal function and elevated serum phosphate, but were not associated with loss of renal α-KL. Moreover, despite falling renal α-KL levels, the increase in FGF23 enhanced urinary fractional excretion of phosphate and reduced serum 1,25VitD3 levels in early and intermediate CKD, though not in advanced CKD. Serum sKL levels also fell significantly over the course of CKD, and renal α-KL was a significant independent determinant of sKL. These results demonstrate that FGF23 levels rise to compensate for renal failure-related phosphate retention in early and intermediate CKD. This enables FGF23-α-KL signaling and a neutral phosphate balance to be maintained despite the reduction in α-KL. In advanced CKD, however, renal α-KL declines further. This disrupts FGF23 signaling, and serum phosphate levels significantly increase, stimulating greater FGF23 secretion. Our results also suggest the serum sKL concentration may be a useful marker of renal α-KL expression levels. 相似文献
16.
Toyama Yoshiro Murase Kimihiko Azuma Masanori Hamada Satoshi Tachikawa Ryo Tanizawa Kiminobu Handa Tomohiro Kubo Takeshi Hitomi Takefumi Oga Toru Hirai Toyohiro Chin Kazuo 《Sleep and biological rhythms》2018,16(1):117-124
Sleep and Biological Rhythms - Obstructive sleep apnea (OSA) is an established factor in the pathogenesis and exacerbation of fatty liver disease. However, randomized controlled trials have failed... 相似文献
17.
Hiroyuki Tsuda Tadashi Inoue Makoto Asamoto Shoji Fukushima Nobuyuki Ito Takehiko Okamura Kazuo Ohtaguro Hiroto Washida Kimihiko Satoh Zahra Amelizad Franz Oesch 《Virchows Archiv. B, Cell pathology including molecular pathology》1988,56(1):307-316
The expression of a number of enzymes involved in drug metabolism, membrane function etc. was compared in hyperplastic and
neoplastic lesions of the rat bladder and in human bladder tumours. Transitional cell carcinomas (TCC) in both rat and Man
were characterized by decreased alkaline phosphatase (ALP) and increased gammaglutamyl transpeptidase (GGT), β-glucuronidase
(β-Gl), succinate dehydrogenase (SD) and glucose-6-phosphate dehydrogenase (G6PD) activities. In addition, binding for antibodies
specific for different cytochrome P-450 species (UT50, PB3a, MC1, MC2) and microsomal epoxide hydrolase (mEHb) was elevated in both murine and human tumours. Comparison of the enzyme phenotype
in hyperplastic lesions induced by freeze ulceration or uracil administration with that in preneoplastic papillary or nodular
hyperplasia (PNH) and TCC suggested, however, that most of the alteration in enzyme content or activity was non-specific and
related to requirements for epithelial cell proliferation. On the other hand, the decreased ALP, and increased GGT and β -
Gl activity appeared more directly related to neoplastic transformation. The results suggested that qualitative differences
exist between reactive hyperplasia and preneoplastic or neoplastic lesions in the urinary bladder. The finding of increased
cytochrome P-450, in clear contrast to the reduction characteristic of preneoplastic hepatic lesions, may be important with
regard to the observed difference in neoplastic transformation between the bladder and liver in response to drug metabolising
enzyme inducers.
Supported by Grants-in-aid for Cancer Research and a Comprehensive 10 Year Strategy for Cancer Control from the Ministry of
Health and Welfare, for Cancer Research and Scientific Research from the Ministry of Education, Science and Culture, and by
a grant from the Deutsche Forschungsgemeinschaft 相似文献
18.
Akashiba Tsuneto Inoue Yuichi Uchimura Naohisa Ohi Motoharu Kasai Takatoshi Kawana Fusae Sakurai Shigeru Takegami Misa Tachikawa Ryo Tanigawa Takeshi Chiba Shintaro Chin Kazuo Tsuiki Satoru Tonogi Morio Nakamura Hiroshi Nakayama Takeo Narui Koji Yagi Tomoko Yamauchi Motoo Yamashiro Yoshihiro Yoshida Masahiro Oga Toru Tomita Yasuhiro Hamada Satoshi Murase Kimihiko Mori Hiroyuki Wada Hiroo Uchiyama Makoto Ogawa Hiromasa Sato Kazumichi Nakata Seiichi Mishima Kazuo Momomura Shin-Ichi 《Sleep and biological rhythms》2022,20(1):5-37
Sleep and Biological Rhythms - The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously... 相似文献
19.
Yoshiki Yasukochi Jun Sakuma Ichiro Takeuchi Kimihiko Kato Mitsutoshi Oguri Tetsuo Fujimaki Hideki Horibe Yoshiji Yamada 《Genomics》2019,111(1):34-42
Recent genome-wide association studies identified genetic variants that confer susceptibility to type 2 diabetes mellitus (T2DM). However, few longitudinal genome-wide association studies of this metabolic disorder have been reported to date. Therefore, we performed a longitudinal exome-wide association study of T2DM, using 24,579 single nucleotide polymorphisms (SNPs) and repeated measurements from 6022 Japanese individuals. The generalized estimating equation model was applied to test relations of SNPs to three T2DM-related parameters: prevalence of T2DM, fasting plasma glucose level, and blood glycosylated hemoglobin content. Three SNPs that passed quality control were significantly (P < 2.26 × 10? 7) associated with two of the three T2DM-related parameters in additive and recessive models. Of the three SNPs, rs6414624 in EVC and rs78338345 in GGA3 were novel susceptibility loci for T2DM. In the present study, the SNP of GGA3 was predicted to be a genetic variant whose minor allele frequency has recently increased in East Asia. 相似文献
20.
Yoshiki Yasukochi Jun Sakuma Ichiro Takeuchi Kimihiko Kato Mitsutoshi Oguri Tetsuo Fujimaki Hideki Horibe Yoshiji Yamada 《Genomics》2019,111(4):520-533
Recent genome-wide association studies have identified various dyslipidemia-related genetic variants. However, most studies were conducted in a cross-sectional manner. We thus performed longitudinal exome-wide association studies of dyslipidemia in a Japanese population. We used ~244,000 genetic variants and clinical data of 6022 Japanese individuals who had undergone annual health checkups for several years. After quality control, the association of dyslipidemia-related phenotypes with 24,691 single nucleotide polymorphisms (SNPs) was tested using the generalized estimating equation model. In total, 82 SNPs were significantly (P < 2.03 × 10?6) associated with dyslipidemia phenotypes. Of these SNPs, four (rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25) and two (rs34902660 of SLC17A3 and rs1042127 of CDSN) were identified as novel genetic determinants of hypo-HDL- and hyper-LDL-cholesterolemia, respectively. A replication study using the cross-sectional data of 8310 Japanese individuals showed the association of the six identified SNPs with dyslipidemia-related traits. 相似文献