全文获取类型
收费全文 | 1399篇 |
免费 | 97篇 |
出版年
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 9篇 |
2018年 | 15篇 |
2017年 | 10篇 |
2016年 | 20篇 |
2015年 | 39篇 |
2014年 | 35篇 |
2013年 | 66篇 |
2012年 | 67篇 |
2011年 | 80篇 |
2010年 | 44篇 |
2009年 | 43篇 |
2008年 | 59篇 |
2007年 | 78篇 |
2006年 | 65篇 |
2005年 | 62篇 |
2004年 | 53篇 |
2003年 | 50篇 |
2002年 | 52篇 |
2001年 | 60篇 |
2000年 | 52篇 |
1999年 | 45篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 17篇 |
1993年 | 16篇 |
1992年 | 51篇 |
1991年 | 33篇 |
1990年 | 36篇 |
1989年 | 38篇 |
1988年 | 33篇 |
1987年 | 31篇 |
1986年 | 22篇 |
1985年 | 18篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 9篇 |
1981年 | 12篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 13篇 |
1976年 | 4篇 |
1974年 | 6篇 |
1971年 | 4篇 |
1967年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有1496条查询结果,搜索用时 15 毫秒
51.
Prostaglandin E prevents indomethacin-induced gastric and intestinal damage through different EP receptor subtypes 总被引:4,自引:0,他引:4
Tomonori Kunikata Hideo Araki Mosanori Takeeda Shinichi Kato Koji Takeuchi 《Journal of Physiology》2001,95(1-6):157-163
Gastrointestinal ulcerogenic effect of indomethacin is causally related with an endogenous prostaglandin (PG) deficiency, yet the detailed mechanism remains unknown. We examined the effect of various PGE analogues specific to EP receptor subtypes on these lesions in rats and mice, and investigated which EP receptor subtype is involved in the protective action of PGE(2). Fasted or non-fasted animals were given indomethacin s.c. at 35 mg/kg for induction of gastric lesions or 10-30 mg/kg for intestinal lesions, and they were killed 4 or 24 h later, respectively. Various EP agonists were given i.v. 10 min before indomethacin. Indomethacin caused hemorrhagic lesions in both the stomach and intestine. Prior administration of 16,16-dimethyl PGE(2) (dmPGE(2)) prevented the development of damage in both tissues, and the effect in the stomach was mimicked by 17-phenyl PGE2 (EP1), while that in the small intestine was reproduced by ONO-NT-012 (EP3) and ONO-AE-329 (EP4). Butaprost (EP2) did not have any effect on either gastric or intestinal lesions induced by indomethacin. Similar to the findings in rats, indomethacin caused gastric and intestinal lesions in both wild-type and knockout mice lacking EP1 or EP3 receptors. However, the protective action of dmPGE(2) in the stomach was observed in wild-type and EP3 receptor knockout mice but not in mice lacking EP1 receptors, while that in the intestine was observed in EP1 knockout as well as wild-type mice but not in the animals lacking EP3 receptors. These results suggest that indomethacin produced damage in the stomach and intestine in a PGE(2)-sensitive manner, and exogenous PGE(2) prevents gastric and intestinal ulcerogenic response to indomethacin through different EP receptor subtypes; the protection in the stomach is mediated by EP1 receptors, while that in the intestine mediated by EP3/EP4 receptors. 相似文献
52.
Pisani Luciana Pellegrini de Castro Glaucia Monteiro Ribeiro Daniel Araki 《Biological trace element research》2020,194(2):627-628
Biological Trace Element Research - 相似文献
53.
Araki K Takakura H Miyajima Y Akashi Y Kawanishi K Kakita S Kondo Y 《The Journal of General and Applied Microbiology》1999,45(4):169-176
During a study on the effect of DL-serine hydroxamate on Corynebacterium glutamicum (JCM1318, a wild strain), a mutant resistant to the drug, strain TO3002, was isolated. This mutant accumulated five Ehrlich's reagent positive fluorescent substances in the culture medium. Two major and one minor fluorescent products were isolated by preparative high-performance liquid chromatography following charcoal column chromatography from the culture supernatant. One major product was identified as anthranilic acid whose molecular ion was confirmed to be 137 by a measurement of liquid chromatography-mass spectrometry (LC-MS), and NMR spectrum coincided with that of anthranilic acid. LC-MS spectra of another major and the minor product showed that they had the same molecular weight of 299. This major product was supported to be N-glucosylanthranilic acid (N-o-carboxyphenyl-1-beta-glucosylamine) by two-dimensional (1)H and (13)C NMR analyses. The minor product was speculated to be an Amadori compound derived from N-glucosylanthranilic acid. N-Glucosylanthranilic acid accumulated in the early phase, then decreased in the late phase of the culture. In contrast, the accumulation of anthranilic acid increased remarkably in the late phase of the fermentation. Based on this phenomenon, it was assumed that N-glucosylanthranilic acid once accumulated was decomposed to form anthranilic acid, at least in large part, with the progress of fermentation. The strain TO3002 showed a leaky requirement for L-tryptophan or indole (but did not for anthranilic acid) and resistance to DL-serine hydroxamate. 相似文献
54.
Y Kimura Y Araki A Takenaka K Igarashi 《Bioscience, biotechnology, and biochemistry》1999,63(5):799-804
The preventive effects of nasunin (delphinidin-3-[4-p-coumaroyl-rhamnosyl(1-->6)glucosid e]-5-glucoside) on paraquat-induced oxidative stress were determined in rats. Decreased food intake and body weight gain and increased lung weight by feeding the rats a diet containing paraquat were clearly suppressed by supplementing nasunin to the paraquat diet. Paraquat feeding increased the concentration of thiobarbituric acid-reactive substances (TBARS) in liver lipids and the atherogenic index, and decreased the liver triacylglycerol level. These effects were also suppressed by supplementing nasunin to the paraquat diet. In addition, catalase activity in the liver mitochondrial fraction was markedly decreased by feeding the paraquat diet, this decrease being partially suppressed by supplementing the paraquat diet with nasunin. These results suggest that nasunin acted preventively against the oxidative stress in vivo that may have been due to active oxygen species formed through the action of paraquat. 相似文献
55.
Regionalization of a simple neural tube is a fundamental event during the development of central nervous system. To analyze in vivo the molecular mechanisms underlying the development of mesencephalon, we ectopically expressed Engrailed, which is expressed in developing mesencephalon, in the brain of chick embryos by in ovo electroporation. Misexpression of Engrailed caused a rostral shift of the di-mesencephalic boundary, and caused transformation of dorsal diencephalon into tectum, a derivative of dorsal mesencephalon. Ectopic Engrailed rapidly repressed Pax-6, a marker for diencephalon, which preceded the induction of mesencephalon-related genes such as Pax-2, Pax-5, Fgf8, Wnt-1 and EphrinA2. In contrast, a mutant Engrailed, En-2(F51rE), bearing mutation in EH1 domain, which has been shown to interact with a co-repressor, Groucho, did not show the phenotype induced by wild-type Engrailed. Furthermore, VP16-Engrailed chimeric protein, the dominant positive form of Engrailed, caused caudal shift of di-mesencephalic boundary and ectopic Pax-6 expression in mesencephalon. These data suggest that (1) Engrailed defines the position of dorsal di-mesencephalic boundary by directly repressing diencephalic fate, and (2) Engrailed positively regulates the expression of mesencephalon-related genes by repressing the expression of their negative regulator(s). 相似文献
56.
Prostaglandin E receptor subtypes involved in stimulation of gastroduodenal bicarbonate secretion in rats and mice. 总被引:4,自引:0,他引:4
K Takeuchi H Ukawa O Furukawa S Kawauchi H Araki Y Sugimoto A Ishikawa F Ushikubi S Narumiya 《Journal of physiology and pharmacology》1999,50(2):155-167
We investigated prostaglandin E (EP) receptor subtypes responsible for the HCO3- stimulatory action of prostaglandin E2 (PGE2) in the gastroduodental mucosa, by examining the effects of various prostanoids with subtype specific EP receptor agonists in rats and those of PGE2 in knockout mice lacking EP1 or EP3 receptors. In rats, gastric HCO3- secretion was stimulated by i.v. administration of PGE2, 17-phenyl PGE2 the selective EP1 agonist as well as sulprostone the EP1 and EP3 agonist, but was not affected by other EP agonists such as butaprost the selective EP2 agonist, ONO-NT-012 the selective EP3 agonist or 11-deoxy PGE1 the EP3 and EP4 agonist. In contrast, the HCO3- secretion in rat duodenums was stimulated by PGE2, sulprostone, ONO-NT-012 as well as 11-deoxy PGE1 but not affected by either 17-phenyl PGE2 or butaprost. The HCO stimulatory effect of sulprostone in the stomach was significantly inhibited by ONO-AE-829, the selective EP1 antagonist. On the other hand, PGE2 applied topically to the mucosa for 10 min caused a dose-dependent increase of HCO3- secretion in both the stomach and duodenum of wild-type mice. The HCO3- stimulatory action of PGE2 in the stomach was also observed dose-dependently in knockout mice lacking EP3-receptors but was absent in EP1-receptor knockout mice, while the stimulatory effect in the duodenum was observed in EP1-receptor knockout mice, similar to wild-type animals, but not in knockout mice lacking EP3-receptors. These results indicate that PGE2 stimulates HCO3- secretion via different EP receptor subtypes in the stomach and duodenum; the former is mediated by EP1-receptors, while the latter mediated by EP3-receptors. 相似文献
57.
Shimada H Kaname T Suzuki M Hitoshi Y Araki K Imaizumi T Yamamura K 《Molecular reproduction and development》1999,52(4):376-382
Markers and the means to detect them are required to monitor the fate of living cells. However, few suitable markers for living cells were known until a green fluorescent protein (GFP) was discovered. We have established mouse embryonic stem (ES) cell lines that express mutant GFP under the chicken beta-actin (CAG) promoter. Using these cell lines, we were able to follow the migration of ES cells during blastocyst formation both in sandwiching and coculture methods, even if only a single ES cell was used. Furthermore, the contribution of ES cells to the inner cell mass (ICM) was easily estimated at the blastocyst stage. We compared sandwiching with coculture aggregation relative to the contribution of the ES cell in the ICM, and the results indicated that there was no difference in the ratios of chimeric embryos having ICM contributed from cultured ES cells. Furthermore, an aggregated single ES cell was able to contribute three or four cells to the ICM at the blastocyst stage. Thus we conclude that one, instead of two, embryos is enough to make aggregation with ES cells, and a single ES cell attached to an embryo is enough to produce germline chimeras. Moreover, we could clearly observe single cell fate during blastocyst formation. This suggests that our established cell line can be used for monitoring single cell fate in vivo. In addition, we have shown that up to five doses of 30 sec of UV irradiation using GFP filters have no effect on the embryonic development. 相似文献
58.
Sld2, Which Interacts with Dpb11 in Saccharomyces cerevisiae, Is Required for Chromosomal DNA Replication 总被引:4,自引:2,他引:2 下载免费PDF全文
Yoichiro Kamimura Hiroshi Masumoto Akio Sugino Hiroyuki Araki 《Molecular and cellular biology》1998,18(10):6102-6109
The DPB11 gene, which genetically interacts with DNA polymerase II (), one of three replicative DNA polymerases, is required for DNA replication and the S phase checkpoint in Saccharomyces cerevisiae. To identify factors interacting with Dbp11, we have isolated sld (synthetically lethal with dpb11-1) mutations which fall into six complementation groups (sld1 to -6). In this study, we characterized SLD2, encoding an essential 52-kDa protein. High-copy SLD2 suppressed the thermosensitive growth defect caused by dpb11-1. Conversely, high-copy DPB11 suppressed the temperature-sensitive growth defect caused by sld2-6. The interaction between Sld2 and Dpb11 was detected in a two-hybrid assay. This interaction was evident at 25°C but not at 34°C when Sld2-6 or Dpb11-1 replaced its wild-type protein. No interaction between Sld2-6 and Dpb11-1 could be detected even at 25°C. Immunoprecipitation experiments confirmed that Dpb11 physically interacts with Sld2. sld2-6 cells were defective in DNA replication at the restrictive temperature, as were dpb11-1 cells. Further, in dpb11-1 and sld2-6 cells, the bubble-shaped replication intermediates formed in the region of the autonomously replicating sequence reduced quickly after a temperature shift. These results strongly suggest the involvement of the Dpb11-Sld2 complex in a step close to the initiation of DNA replication. 相似文献
59.
Takahashi N Yamada W Masuda K Araki H Tsukamoto Y Galinha A Sautès C Kato K Shimada I 《Glycoconjugate journal》1998,15(9):905-914
N-glycans of a recombinant mouse soluble Fc receptor II (sFcRII) expressed in baby hamster kidney cells were released from glycopeptides by digestion with glycoamidase A (from sweet almond), and the reducing ends of the oligosaccharides were reductively aminated with 2-aminopyridine. The derivatized N-glycans were separated and structurally identified by a three-dimensional high-performance liquid chromatography (HPLC) mapping technique on three kinds of HPLC columns [Takahashi, et al. (1995) Anal. Biochem. 226: 139–46]. Eighteen different major N-glycan structures were identified, of which six were neutral (45%), five mono-sialyl (49%), one di-sialyl (4.6%), five tri-sialyl (1.1%), and one tetra-sialyl (0.3%). All N-glycan structures determined were complex type with fucosylation at the N-acetylglucosamine residue of the reducing end, and N-acetylneuraminic acid, when present, was -(2,3)-linked. The existence of a unique structure containing both N-acetylgalactosamine and -(2,3)-N-acetylneuraminic acid residues at the reducing ends, as below, was confirmed by MALDI-TOF mass spectrometry. 相似文献
60.
Takashi Araki Yasushi Kobayashi Hidetaka Kaya Masaki Iwabuchi 《Journal of plant research》1998,111(2):277-281
Transition from vegetative to reproductive development (flowering) is one of the most important decisions during the post-embryonic
development of flowering plants. More than twenty loci are known to regulate this process inArabidopsis. Some of these flowering-time genes may act at the shoot apical meristem to regulate its competence to respond to floral
inductive signals and floral evocation. Genetic and phenotypic analyses of mutants suggest that the late-flowering geneFT may be a good candidate for such genes. To test this, we have cloned theFT gene using aFT-deficiency line associated with a T-DNA insertion. Cloned genes and loss-of-function mutants in hand, it is now possible
to analyse the role ofFT and other genes in flowering at the biochemical and cellular levels as well as at the genetic level. The deduced FT protein
has homology with TFL1 and CEN proteins believed to be involved in regulation of inflorescence meristem identity. Phylogenetic
analysis suggests that theFT group and theTFL1/CEN group of genes diverged before the diversification of major angiosperm clades. This raises the interesting question of the
evolutionary relationship between the regulation of vegetative/reproductive switching in the shoot apical meristem and the
regulation of inflorescence architecture in angiosperms.
The extended abstract of a paper presented at the 13th International Symposium in Conjugation with Award of the International
Prize for Biology “Fronitier of Plant Biology” 相似文献