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51.
Zhang MR Kumata K Maeda J Haradahira T Noguchi J Suhara T Halldin C Suzuki K 《Journal of medicinal chemistry》2007,50(4):848-855
To image the peripheral-type benzodiazepine receptor (PBR) in vivo, we previously developed two positron emission tomography (PET) ligands, N-(2-[11C],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([11C]1a) and its [18F]fluoroethyl analogue ([18F]1b), for the investigation of PBR in the living human brain. This time, using 1a as a leading compound, we designed two novel iodinated analogues, N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide (3a) and N-(2,5-dimethoxybenzyl)-N-(5-iodo-2-phenoxyphenyl)acetamide (3b) for the PBR imaging. Ligands 3 were synthesized by the iodination of tributystannyl precursors 10. Radiolabeling for 3 with 131I was carried out by the reaction of 10 with [131I]NaI using H2O2 as an oxidizing agent. In vitro competition experiments determined that 3a exhibited both high affinity and selectivity for PBR (IC50: 7.8 nM) vs CBR (>1 microM). Biodistribution study in mice determined that [131I]3a had a high radioactivity level (1.69% dose/g) in the brain, and its distribution pattern in the brain was consistent with the known distribution of PBR in rodents. Ex vivo autoradiography of the rat brain gave visual evidence that [131I]3a was a potent and specific radioligand for PBR. 相似文献
52.
Katsushi Kumata Makoto Takei Masanao Ogawa Joji Yui Akiko Hatori Kazutoshi Suzuki Ming‐Rong Zhang 《Journal of labelled compounds & radiopharmaceuticals》2010,53(2):53-57
Recent studies revealed that thalidomide (1) has unique and broad pharmacological effects on multi‐targets although the application of 1 in therapy is still controversial. In this study, we synthesized nitrogen‐13‐labeled thalidomide ([13N]1) as a potential positron emission tomography (PET) probe using no‐carrier‐added [13N]NH3 as a labeling agent. By use of an automated system, [13N]1 was prepared by reacting N‐phthaloylglutamic anhydride (2) with [13N]NH3, following by cyclization with carbonyldiimidazole in a radiochemical yield of 56±12% (based on [11N]NH3, corrected for decay) and specific activity of 49±24 GBq/µmol at the end of synthesis (EOS). At EOS, 570–780 MBq (n=7) of [13N]1 was obtained at a beam current of 15 µA after 15 min proton bombardment with a synthesis time of 14 min from the end of bombardment. Using a small animal PET scanner, preliminary biodistribution of [13N]1 in mice was examined. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
53.
Hepatocyte growth factor ameliorates renal hemodynamic disorder after ischemia/reperfusion 总被引:4,自引:0,他引:4
Nakatani T Kim T Uchida J Kumata N Kawashima H Sugimura K 《International journal of molecular medicine》2002,10(2):217-219
Ischemic injury of the transplanted kidney is one of the causes of reduced graft survival. The purpose of the present experiment was to examine whether hepatocyte growth factor (HGF) would improve acute renal hemodynamic recovery immediately after cold ischemia. Addition of HGF to the preservation solution during 3 h cold ischemia of dog kidney accelerated both recovery of renal blood flow and glomerular filtration rate (GFR). It is suggested that HGF may be useful for preservation of excised kidney for transplantation. As intrarenal arterial infusion of HGF in normal dog kidney had no effects on renal hemodynamics, mechanisms other than direct vasodilator action of HGF appear to be operating in the protection. 相似文献
54.
Yoshiyuki Kumata Nobuyuki Asada Gordon M. Parker Junji Furukawa 《Macromolecular chemistry and physics.》1970,136(1):291-296
The asymmetric-selection polymerization of styrene oxide was investigated by using diethylzinc/menthol system as catalyst. Monomer consumption was found to follow a second order kinetic, whereas developing of the optical rotation of the remaining monomer followed a first order reaction scheme. This phenomenon is accounted for by the assumption that the polymerization consists of rapid initiation followed by slow stepwise growth. Two moles of monomer participate in the polymerization, one of which is polymerized and the other is responsible for activation of the catalyst. The asymmetric ability of the catalyst is arising from the menthoxyl group but not from propylene oxide complexed to the catalyst. 相似文献
55.
Nagira M Tomita M Mizuno S Kumata M Ayabe T Hayashi M 《Drug metabolism and pharmacokinetics》2006,21(3):230-237
We previously established a in vitro system for assessing early ischemia/reperfusion injury using monolayers of human intestinal epithelial cell line Caco-2, in which lipid peroxidation caused by tertiary-butylhydroperoxide (t-BuOOH), a lipid peroxidation inducer, acts as a trigger of the injury. By now, we have shown that superoxide anion participates in the opening of tight junctions (TJ) induced by reoxygenation following the induction of lipid peroxidation by t-BuOOH at a low concentration. The present objectives are to elucidate the dysfunction of P-glycoprotein (P-gp) in addition to the opening of TJ by t-BuOOH at a high concentration condition using rhodamine123 (Rho123) as a P-gp substrate and cyclosporine A (CyA) as a P-gp inhibitor. Also, we compared the inhibition effect of lutein and other compounds such as biliverdin as a radical scavenger on the opening of TJ and the dysfunction of P-gp. t-BuOOH at a high concentration increased the permeability of Rho123 in the apical to basal direction and decreased basal to apical direction when compared with control conditions. t-BuOOH at a high concentration showed no significant difference between directional transport of Rho123 and no inhibition was observed in the permeability of both directions by CyA. The staining intensity of Western blot was decreased by t-BuOOH at a high concentration. Although lutein and the other compounds had recovery effects on the opening of TJ and P-gp dysfunction induced by t-BuOOH, lutein is more advantageous than other compounds since it has effective effects at the lower concentration. In conclusion, the barrier dysfunction such as the inhibition of P-gp in addition to the opening of TJ was induced by t-BuOOH at a high concentration condition. The above two barrier dysfunctions was ameliorated by antioxidant such as lutein and biliverdin. 相似文献
56.
57.
Ji-yun Sun Katsushi Kumata Zhen Chen Yi-ding Zhang Jia-hui Chen Akiko Hatori Hua-long Fu Jian Rong Xiao-yun Deng Tomoteru Yamasaki Lin Xie Kuan Hu Masayuki Fujinaga Qing-zhen Yu Tuo Shao Thomas Lee Collier Lee Josephson Yi-han Shao Yun-fei Du Lu Wang Hao Xu Ming-rong Zhang Steven H Liang 《Acta pharmacologica Sinica》2021,42(3):491-498
N-methyl-D-aspartate receptors(NMDARs)play critical roles in the physiological function of the mammalian central nervous system(CNS),including learning,memory,and synaptic plasticity,through modulating excitatory neurotransmission.Attributed to etiopathology of various CNS disorders and neurodegenerative diseases,GluN2B is one of the most well-studied subtypes in preclinical and clinical studies on NMDARs.Herein,we report the synthesis and preclinical evaluation of two11C-labeled GluN2B-selective negative allosteric modulators(NAMs)containing N,N-dimethyl-2-(1H-pyrrolo[3,2-b]pyridin-1-yl)acetamides for positron emission tomography(PET)imaging.Two PET ligands,namely[11C]31 and[11C]37(also called N2B-1810 and N2B-1903,respectively)were labeled with[11C]CH3I in good radiochemical yields(decay-corrected 28%and 32%relative to starting[11C]CO2,respectively),high radiochemical purity(>99%)and high molar activity(>74 GBq/μmol).In particular,PET ligand[11C]31 demonstrated moderate specific binding to GluN2B subtype by in vitro autoradiography studies.However,because in vivo PET imaging studies showed limited brain uptake of[11C]31(up to 0.5 SUV),further medicinal chemistry and ADME optimization are necessary for this chemotype attributed to low binding specificity and rapid metabolism in vivo. 相似文献
58.
Tomoteru Yamasaki Masayuki Fujinaga Joji Yui Yoko Ikoma Akiko Hatori Lin Xie Hidekatsu Wakizaka Katsushi Kumata Nobuki Nengaki Kazunori Kawamura Ming-Rong Zhang 《Journal of cerebral blood flow and metabolism》2014,34(4):606-612
Because of its role in multiple central nervous system (CNS) pathways, metabotropic glutamate receptor type 1 (mGluR1) is a crucial target in the development of pharmaceuticals for CNS disorders. N-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]-methylbenzamide ([11C]ITDM) was recently developed as a positron emission tomography (PET) ligand for mGluR1. To devise a method for measurement of the binding potential (BPND) of [11C]ITDM to mGluR1, reference tissue methods aimed at replacing measurement of the arterial input function are desirable. In this study, we evaluated a noninvasive quantification method of mGluR1 with [11C]ITDM, demonstrating its accuracy using Huntington disease model R6/2 mice. The BPND measurements based on the Logan reference (Logan Ref) method have closely approximated that based on the arterial input method. We performed PET analysis with Logan Ref to assess its accuracy in quantifying the decline of mGluR1 expression in R6/2 mice. Significant decreases in BPND values in R6/2 mice were detected in cerebellum, thalamus, striatum, and cingulate cortex. We compared autoradiographs of R6/2 mouse brain sections with immunohistochemical images, and found a close correlation between changes in radioactive signal intensity and degree of mGluR1 expression. In conclusion, [11C]ITDM-PET is a promising tool for in vivo quantification of mGluR1 expression. 相似文献
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