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301.
Yukifumi Uesono Akio Toh-e Yoshiko Kikuchi Tomoyuki Araki Takushi Hachiya Chihiro K. Watanabe Ko Noguchi Ichiro Terashima 《Genetics》2016,202(3):997-1012
Action mechanisms of anesthetics remain unclear because of difficulty in explaining how structurally different anesthetics cause similar effects. In Saccharomyces cerevisiae, local anesthetics and antipsychotic phenothiazines induced responses similar to those caused by glucose starvation, and they eventually inhibited cell growth. These drugs inhibited glucose uptake, but additional glucose conferred resistance to their effects; hence, the primary action of the drugs is to cause glucose starvation. In hxt0 strains with all hexose transporter (HXT) genes deleted, a strain harboring a single copy of HXT1 (HXT1s) was more sensitive to tetracaine than a strain harboring multiple copies (HXT1m), which indicates that quantitative reduction of HXT1 increases tetracaine sensitivity. However, additional glucose rather than the overexpression of HXT1/2 conferred tetracaine resistance to wild-type yeast; therefore, Hxts that actively transport hexoses apparently confer tetracaine resistance. Additional glucose alleviated sensitivity to local anesthetics and phenothiazines in the HXT1m strain but not the HXT1s strain; thus, the glucose-induced effects required a certain amount of Hxt1. At low concentrations, fluorescent phenothiazines were distributed in various membranes. At higher concentrations, they destroyed the membranes and thereby delocalized Hxt1-GFP from the plasma membrane, similar to local anesthetics. These results suggest that the aforementioned drugs affect various membrane targets via nonspecific interactions with membranes. However, the drugs preferentially inhibit the function of abundant Hxts, resulting in glucose starvation. When Hxts are scarce, this preference is lost, thereby mitigating the alleviation by additional glucose. These results provide a mechanism that explains how different compounds induce similar effects based on lipid theory. 相似文献
302.
Heme synthase (ferrochelatase) catalyzes the removal of iron from heme and demetalation of metalloporphyrins 总被引:2,自引:0,他引:2
Taketani S Ishigaki M Mizutani A Uebayashi M Numata M Ohgari Y Kitajima S 《Biochemistry》2007,46(51):15054-15061
The red pigments in meat products, including cooked cured ham, arise from the reaction of myoglobin with nitric oxide generated from exogenous nitrite. Since carcinogenic nitrosoamines may be generated by the treatment of meats with nitrite, the production of nitrite-free meat products is an attractive alternative. Raw dry-cured (Parma) hams are produced by the treatment of meats with salts other than nitrite. Analysis of pigments in raw dry-cured hams reveals that the main pigment is zinc protoporphyrin, suggesting that the conversion of heme to zinc protoporphyrin occurs via an iron-removal reaction from myoglobin heme during the processing of raw hams. Purification of the iron-removal enzyme showed that it was identical to ferrochelatase. Recombinant ferrochelatase in combination with NADH-cytochrome b5 reductase catalyzed NADH-dependent iron-removal reaction from hemin and hemoproteins. Metal ions such as zinc and cobalt were also removed from the corresponding metalloporphyrins. The addition of zinc ions led to the formation of zinc protoporphyrin. In cultured cells, the conversion of zinc mesoporphyrin to mesoheme was observed to be dependent on ferrochelatase and could be markedly induced during erythroid differentiation. This is the first demonstration of a new enzyme reaction, the reverse reaction of ferrochelatase, which may contribute to a new route of the recycling of protoporphyrin and heme in cells. 相似文献
303.
Identification of genetic loci affecting amylose content and agronomic traits on chromosome 4A of wheat 总被引:20,自引:0,他引:20
E. Araki H. Miura S. Sawada 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1999,98(6-7):977-984
Chromosome 4A of wheat carries the Wx-B1 gene encoding the granule-bound starch synthase involved in amylose synthesis in the endosperm. To determine the pleiotropic
effects of this locus and effects of independent QTLs on agronomic traits, genetical analysis of chromosome 4A was conducted
using 98 single-chromosome recombinant substitution lines derived from a cross of Chinese Spring and Chinese Spring (Kanto107
4A) with a low amylose content due to the null Wx-B1b allele. For amylose content, most of the genetic variation was explained by the allelic difference at the Wx-B1 locus. An additional QTL of minor effect was mapped in the 6.2-cM Xbcd1738/Xcdo1387 interval on the short arm, where the allele from Kanto107 led to an increase in amylose content. Field trials over two seasons
revealed a pleiotropic effect of Wx-B1, or else the effect of a closely linked QTL, on ear emergence time. A QTL linked to Wx-B1 was detected for plant height. For plant yield and its components, there was no evidence for significant main effects associated
with Wx-B1 or adjacent regions. One plant-yield QTL was identified by RFLP markers on the short arm and this was identical to QTLs controlling
spikelet number/ear and grain weight/ear. At these QTLs for agronomic traits, alleles from Kanto107 contributed to an earlier
emergence time, a height reduction and an yield increase.
Received: 10 August 1998 / Accepted: 3 November 1998 相似文献
304.
Functional absence of FADD in PLC/PRF/5 hepatoma cells: possible involvement in the transformation to hepatoma in HBV-infected hepatocytes. 总被引:6,自引:0,他引:6
A Suzuki T Araki M Miura Y Tsutomi 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1999,221(1):72-79
The death receptor Fas transduces apoptotic death signaling upon stimulation by Fas ligand and plays a key role in viral hepatitis. When hepatitis-B virus (HBV) infects hepatocytes, the Fas ligand/Fas system responds as the triggering machinery of hepatitis. However, some HBV-infected cells may circumvent Fas-mediated apoptosis and transform to hepatoma cells, as do PLC/PRF/5 hepatoma cells. Therefore, in the present study, we used PLC/PRF/5 hepatoma cells to investigate this ability to avoid Fas-mediated apoptosis. When the cells were treated with an agonistic Fas antibody, they showed resistance to Fas-mediated apoptosis. In contrast, HepG2 cells of the same hepatoma line succumbed. Caspase 3 and 8, which are essential regulators for Fas-mediated cell death, were expressed in both hepatoma cell lines, but only HepG2 cells showed activation of the caspases. A comparison study of expression of other death-associated factors between PLC/PRF/5 and HepG2 cells revealed no apparent differences. However, Far-Western blotting analysis using the Fas death domain (FDD) showed a significant difference. Molecular weight comparison and immunoblotting analysis revealed that PLC/PRF/5 cells lack the FDD-associated protein FADD. In addition, FDD-injected HepG2 cells showed a resistance to Fas-mediated apoptosis, and PLC/PRF/5 cells acquired Fas-sensitivity by FADD injection. Here, we propose that a functional absence of FADD is one of the pathways for the carcinogenesis of HBV-infected hepatocytes. 相似文献
305.
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
306.
We determined the complete nucleotide sequence of the mitochondrial genome (except for a portion of the putative control
region) for a deep-sea fish, Gonostoma gracile. The entire mitochondrial genome was purified by gene amplification using long polymerase chain reaction (long PCR), and the
products were subsequently used as templates for PCR with 30 sets of newly designed, fish-universal primers that amplify contiguous,
overlapping segments of the entire genome. Direct sequencing of the PCR products showed that the genome contained the same
37 mitochondrial structural genes as found in other vertebrates (two ribosomal RNA, 22 transfer RNA, and 13 protein-coding
genes), with the order of all rRNA and protein-coding genes, and 19 tRNA genes being identical to that in typical vertebrates.
The gene order of the three tRNAs (tRNAGlu, tRNAThr, and tRNAPro) relative to cytochrome b, however, differed from that determined in other vertebrates. Two steps of tandem duplication of gene regions, each followed
by deletions of genes, can be invoked as mechanisms generating such rearrangements of tRNAs. This is the first example of
tRNA gene rearrangements in a bony fish mitochondrial genome.
Received August 5, 1998; accepted February 19, 1999. 相似文献
307.
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
308.
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
309.
310.
Y. Fujii T. Fujiwara Y. Koide I. Hasan S. Sugawara S. Rajia S. M. A. Kawsar D. Yamamoto D. Araki R. A. Kanaly Y. Ogawa H. Fujita Y. Ozeki 《Glycoconjugate journal》2017,34(1):85-94
An N-acetyl sugar-binding lectin (termed iNoL) displaying cytotoxic activity against human cancer cells was isolated from the slipper lobster Ibacus novemdentatus (family Scyllaridae). iNoL recognized monosaccharides containing N-acetyl group, and glycoproteins (e.g., BSM) containing oligosaccharides with N-acetyl sugar. iNoL was composed of five subunits (330, 260, 200, 140, and 30 kDa), which in turn consisted of 70-, 40-, and 30-kDa polypeptides held together by disulfide bonds. Electron microscopic observations and gel permeation chromatography indicated that iNoL was a huge (500-kDa) molecule and had a polygonal structure under physiological conditions. iNoL displayed cytotoxic (apoptotic) effects against human cancer cell lines MCF7 and T47D (breast), HeLa (ovarian), and Caco2 (colonic), through incorporation (internalization) into cells. The lectin was transported into lysosomes via endosomes. Its cytotoxic effect and incorporation into cells were inhibited by the co-presence of N-acetyl-D-mannosamine (ManNAc). Treatment of HeLa cells with iNoL resulted in DNA fragmentation and chromatin condensation, through activation of caspase-9 and ?3. In summary, the novel crustacean lectin iNoL is incorporated into mammalian cancer cells through glycoconjugate interaction, and has cytotoxic (apoptotic) effects. 相似文献