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71.
Nishiyama T Ohnuma T Inoue Y Kishi T Ogura K Hiratsuka A 《Biochemical and biophysical research communications》2008,371(2):247-250
Menadione (2-methyl-1,4-naphthoquine), also known as vitamin K3, has been widely used as a model compound in the field of oxidative stress-related research. The metabolism of menadione has been studied, and it is known that menadione undergoes a two-electron reduction by NAD(P)H:Quinone oxidoreductase 1 (NQO1) after which the reduced form of menadione (2-methyl-1,4-naphthalenediol, menadiol) is glucuronidated and excreted in urine. To investigate which human UDP-glucuronosyltransferase (UGT) isoforms participate in the glucuronidation of menadiol reduced by NQO1 from menadione, we first constructed heterologously expressed NQO1 in Sf9 cells and tested the menadiol glucuronidating activity of 16 human recombinant UGT isoforms. Of the 16 UGT isoforms, UGTs 1A6, 1A7, 1A8, 1A9, and 1A10 catalyzed menadiol glucuronidation, and, of these, UGTs 1A6 and 1A10 catalyzed menadiol glucuronidation at much higher rates than the other UGTs. Menadiol was regioselectively glucuronidated in the manner of 4-position > 1-position by UGTs 1A7, 1A8, 1A9, and 1A10. In contrast to these UGTs, only UGT1A6 exhibited 1-menadiol-preferential glucuronidating activity. The results suggest possible detoxification pathways for quinones via NQO1 reduction followed by UGT glucuronidation. 相似文献
72.
Keiko Funato Teruko Imai Kenichiro Nakashima Masaki Otagiri 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,757(2):229-235
This paper describes a new method of high-performance liquid chromatography with chemiluminescence detection for the analysis of penbutolol (PB) and its main metabolite, 4-hydroxy penbutolol (4-OH PB) in rat plasma. 4-Dimethylaminosulfonyl-7-(N-chloroformylmethyl-N-methyl) amino-2,1,3-benzoxadiazole (DBD-COCl) was used as a fluorogenic labeling reagent. A mixture of hydrogen peroxide and bis[4-nitro-2-(3,6,9-trioxadecyloxycarbonyl)phenyl]oxalate (TDPO) in acetonitrile was used as a post-column chemiluminogenic reagent. The derivatives of PB and 4-OH PB with DBD-COCl were separated by isocratic effluent with 0.01 M imidazole buffer (pH 7.0)–acetonitrile within 10 min. The detection limits of the proposed method for PB and 4-OH PB were 9.9 and 15 fmol on column, respectively. After intravenous administration of PB in rats, its plasma concentration profiles of PB and 4-OH PB were determined by the proposed method. PB was demonstrated to be rapidly metabolized to 4-OH PB at the same rate as cardiac output. 相似文献
73.
74.
Aiko Shinko Takashi Agari Masahiro Kameda Takao Yasuhara Akihiko Kondo Judith Thomas Tayra Kenichiro Sato Tatsuya Sasaki Susumu Sasada Hayato Takeuchi Takaaki Wakamori Cesario V. Borlongan Isao Date 《PloS one》2014,9(7)
In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson’s disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1–2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness and safety. 相似文献
75.
Toll‐like receptors 2 and 3 enhance melanogenesis and melanosome transport in human melanocytes 下载免费PDF全文
Saaya Koike Kenshi Yamasaki Takeshi Yamauchi Mai Inoue Ryoko Shimada‐Ohmori Kenichiro Tsuchiyama Setsuya Aiba 《Pigment cell & melanoma research》2018,31(5):570-584
Because little is known about how the innate immune response influences skin pigmentation, we examined whether Toll‐like receptor (TLR) agonists participate in melanogenesis and melanosome transportation. We observed that TLR2/2 agonist HKLM and TLR3 agonist Poly(I:C) increased the amount of extracellular melanin from primary human epidermal melanocytes. HKLM, but not Poly(I:C), increased the melanogenic genes such as tyrosinase and dopachrome tautomerase. Poly(I:C) increased the expression of Rab27A, a molecule that facilitates melanosome transport to perimembranous actin filament. UVB irradiation induced Rab27A and melanosome transportation in a similar manner of Poly(I:C). SiRNA for TLR3 or Rab27A suppressed the perimembranous accumulation of Gp100‐positive vesicles in melanocytes and decreased melanin transfer to neighboring keratinocytes induced by both Poly(I:C) and UVB. These results suggest that the microenvironment in the epidermis and innate immune stimuli, such as microbiome and ultraviolet represented here by TLR2 and TLR3 agonists, could affect the melanogenesis in human melanocytes. 相似文献
76.
Kei Yabuki Joji Haratake Yojiro Tsuda Eisuke Shiba Hiroshi Harada Kenji Yorita Kazuyoshi Uchihashi Atsuji Matsuyama Keiji Hirata Masanori Hisaoka 《Biological trace element research》2018,185(1):36-47
Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000 mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions. 相似文献
77.
Suleiman M. Saidi Yoshio Lijima William K. Sang Anderson K. Mwangudza Joseph O. Oundo Kenichiro Taga Masanori Aihara Kenichi Nagayama Hiroyuki Yamamoto Peter G. Waiyaki Takeshi Honda 《Microbiology and immunology》1997,41(10):773-778
Diarrheal diseases are major causes of morbidity and mortality among children in developing countries. We have analyzed the causative agents of diarrhea in children under five years of age who resided in rural environments but attended a hospital in Malindi, a coastal town in Kenya. Bacterial diarrhea was found in 239 (27.7%) of 862 patients with diarrhea. Diarrheagenic Escherichia coli, including enteropathogenic, enterotoxigenic, and enterohaemorrhagic strains, was isolated from 119 (13.8%) patients, followed by Salmonella spp. (63 cases, 7.3%) and Shigella spp. (56 cases, 6.5%). Intestinal parasites were found in 109 (12.6%) of the patients. Entamoeba histolytica and Giardia lamblia were found in 67 (7.8%) and 42 (4.9%) of the cases, respectively. Rotavirus was found in 69 (16.1%) of 428 cases, a part of the 862 cases. Significant differences in age distribution were seen in diarrheal cases due to Campylobacter spp., G. lamblia, and rotavirus. No significant seasonal incidence of specific pathogens was found, but the number of diarrheal patients was significantly correlated to rainfall. Drinking water was contaminated with bacteria at concentrations ranging from 103 to 106 CFU/ml in 98% of the households and by coliform bacteria at concentrations of 102 to 105 CFU/ml in 72% of the households. These results suggest that the main routes of infection may be contaminated drinking water and fecal-oral transmission of enteric pathogens. Consequently, we propose that the enhancement of hygienic practice through health education is a feasible control measure of diarrhea in the study area. 相似文献
78.
Kenichiro Inoue Shinichi Ueda Hidekazu Nayeshiro Nobuharu Moritome Hiroyuki Inouye 《Phytochemistry》1984,23(2):312-318
Administration of p13C- and p2H-labelled precursors to Streptocarpus dunnii cell cultures demonstrated that the naphthoquinones formed through aunique prenylation mode are biosynthesized via 4-(2'-carboxyphenyl)-4-oxobutanoic acid, 1,4-dihydroxy-2-naphthoic acid, lawsone and lawsone 2-prenyl ether, and that the anthraquinones are biosynthesized through prenylation of 2-carboxy-4-oxo-1-tetralone at the carboxy-bearing carbon atom to form 2-carboxy-2-prenyl-4-oxo-1-tetralone,or through ipso attack of the prenyl group on the corresponding carbon atom of 1,4-dihydroxy-2-naphthoic acid. 相似文献
79.
80.
Maki Fukami Erina Suzuki Yoko Izumi Tomohiro Torii Satoshi Narumi Maki Igarashi Mami Miyado Momori Katsumi Yasuko Fujisawa Kazuhiko Nakabayashi Kenichiro Hata Akihiro Umezawa Yoichi Matsubara Junji Yamauchi Tsutomu Ogata 《Journal of cellular and molecular medicine》2017,21(10):2623-2626
The human genome encodes ~750 G‐protein‐coupled receptors (GPCRs), including prokineticin receptor 2 (PROKR2) involved in the regulation of sexual maturation. Previously reported pathogenic gain‐of‐function mutations of GPCR genes invariably encoded aberrant receptors with excessive signal transduction activity. Although in vitro assays demonstrated that an artificially created inactive mutant of PROKR2 exerted paradoxical gain‐of‐function effects when co‐transfected with wild‐type proteins, such a phenomenon has not been observed in vivo. Here, we report a heterozygous frameshift mutation of PROKR2 identified in a 3.5‐year‐old girl with central precocious puberty. The mutant mRNA escaped nonsense‐mediated decay and generated a GPCR lacking two transmembrane domains and the carboxyl‐terminal tail. The mutant protein had no in vitro signal transduction activity; however, cells co‐expressing the mutant and wild‐type PROKR2 exhibited markedly exaggerated ligand‐induced Ca2+ responses. The results indicate that certain inactive PROKR2 mutants can cause early puberty by enhancing the functional property of coexisting wild‐type proteins. Considering the structural similarity among GPCRs, this paradoxical gain‐of‐function mechanism may underlie various human disorders. 相似文献