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101.
Nagamine T Nakazato K Suzuki K Kusakabe T Sakai T Oikawa M Satoh T Kamiya T Arakawa K 《Biological trace element research》2007,117(1-3):115-126
This study undertook the analysis of tissue cadmium (Cd) distribution using in-air micro-particle-induced X-ray emission (PIXE)
and the examination of the involvement of metal ions in parenteral Cd toxicity. A mouse was injected intraperitoneally with
3 mg/kg body weight of CdCl2 thrice weekly. After 27 wk, the liver and kidney were excised and fixed in 10% formalin solution for 4 h and then embedded
in paraffin. Thin paraffin sections were used to analyze trace elements with in-air micro-PIXE and to examine metallothionein
protein and histological changes. Cd distribution was determined by micro-PIXE in the liver and renal cortex of the Cd-exposed
mouse, and the net Cd count was higher in the liver than in the renal cortex. The net iron (Fe) count was higher in the liver
of the Cd-exposed mouse compared to the control, and an opposite tendency was observed in the renal cortex. Wide cellular
Cd distribution was demonstrated in the liver and renal cortex of the chronic Cd-exposed mouse compared to the control. Metallothionein
staining was increased by chronic exposure to Cd both in the liver and kidney, and nephrotoxicity was more apparent than hepatotoxicity.
The modification of tissue Fe and calcium distribution by an intraperitoneal injection of Cd might be involved in Cd-induced
toxicity. 相似文献
102.
Kobayashi M Abiru N Arakawa T Fukushima K Zhou H Kawasaki E Yamasaki H Liu E Miao D Wong FS Eisenbarth GS Eguchi K 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(4):2082-2088
Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes that contains two distinct CD4 epitopes (B:9-16 and B:13-23). One of the two epitopes, B:13-23, overlaps with a CTL epitope (B:15-23). In this study, we report that the elimination of the CTL epitope from the B:9-23 peptide by amino acid substitution (with alanine) at positions B:16 and 19 (A16,19 altered peptide ligand) or truncation of the C-terminal amino acids from the peptide (B:9-21), neither of which stimulated the proliferation of insulin B:15-23 reactive CD8 T cells, provided significant intranasally induced suppression of diabetes when coadministered with a potent mucosal adjuvant cholera toxin (CT). Intranasal treatment with A16,19 resulted in the elimination of spontaneous insulin autoantibodies, significant inhibition of insulitis and remission from hyperglycemia, and prevented the progression to diabetes. Intranasal administration of native B:9-23/CT or B:11-23/CT resulted in a significant enhancement of insulin autoantibody expression and severity of insulitis and failed to prevent diabetes. Our present study indicates that elimination of the CTL epitope from the B:9-23 peptide was critically important for mucosally induced diabetes prevention. The A16,19 altered peptide ligand, but not other native insulin peptides, suppresses insulin autoantibodies associated with protection from and remission of diabetes. 相似文献
103.
Hayashi A Hayashi H Chiba T Sasayama S Onozaki K 《Cancer immunology, immunotherapy : CII》2007,56(4):555-562
In order to study the effect of glycosylation on its biological activities and to develop tumor necrosis factor α (TNFα) with
less deleterious effects, N-acetylneuraminic acid (NeuAc) with a C9 spacer was chemically coupled to human recombinant TNFα. NeuAc-coupled TNFα (NeuAc-TNFα)
exhibited reduced activities in vitro by about threefold compared to native TNFα. In this study, we examined a variety of
TNFα activities in vivo. NeuAc-TNFα reduced activities in the up-regulation of serum levels of IL-6 and NOx, but comparable
activity as native TNFα in the down-regulation of the serum level of glucose. However, NeuAc-TNFα was more potent than TNFα
in the up-regulation of the serum level of serum amyloid A (SAA). NeuAc-TNFα was less toxic to mice. In addition, NeuAc-TNFα
exhibited an augmented anti-tumor activity against Meth-A fibrosarcoma without hemorrhagic necrosis. These results indicate
that coupling with NeuAc enabled us to develop neoglycoTNFα with selective activities in vivo, including enhanced anti-tumor
activity but reduced toxicity. 相似文献
104.
Hayashi A Chiba T Hayashi H Sasayama S Ishiguro T Onozaki K 《Cancer immunology, immunotherapy : CII》2007,56(4):545-553
In order to study the effect of glycosylation on its biological activities, and to develop TNFα with less deleterious effects,
recombinant human TNFα was chemically coupled with N-acetylneuraminic acid (NeuAc). NeuAc with C9 spacer was coupled to TNFα by acyl azide method. Two glycosylated TNFαs, designated
L NeuAc-TNFα and H NeuAc-TNFα, were purified by anion-exchange chromatography. NeuAc coupling to TNFα was confirmed by lectin
blotting. Average number of carbohydrate molecules introduced per molecule of L NeuAc-TNFα and H NeuAc-TNFα were estimated
to be 1.0 and 1.5, respectively. We examined a variety of TNFα activities in vitro, including antiproliferative or cytotoxic
activities to tumor cells, proliferative effect on fibroblast cells, stimulatory effects on IL-6 production by melanoma cells
and NF-κB activation in hepatoma cells. L NeuAc-TNFα and H NeuAc-TNFα exhibited reduced activities about 1/3 and 1/10 as compared
to native TNFα in all the activities performed in vitro. 相似文献
105.
Shibayama K Wachino J Arakawa Y Saidijam M Rutherford NG Henderson PJ 《Molecular microbiology》2007,64(2):396-406
gamma-Glutamyltranspeptidase (GGT) is a periplasmic enzyme of Helicobacter pylori implicated in its pathogenesis towards mammalian cells. We have cloned and expressed the H. pylori strain 26695 recombinant GGT protein in Escherichia coli and purified it to homogeneity. The purified protein exhibited hydrolysis activity with very high affinities for glutamine and glutathione shown by apparent K(m) values lower than 1 muM. H. pylori cells were unable to take up extracellular glutamine and glutathione directly. Instead, these substances were hydrolysed to glutamate by the action of GGT outside the cells. The glutamate produced was then transported by a Na(+)-dependent reaction into H. pylori cells, where it was mainly incorporated into the TCA cycle and partially utilized as a substrate for glutamine synthesis. These observations show that one of the principle physiological functions of H. pylori GGT is to enable H. pylori cells to utilize extracellular glutamine and glutathione as a source of glutamate. As glutamine and glutathione are important nutrients for maintenance of healthy gastrointestinal tissue, their depletion by the GGT enzyme is hypothesized to account for the damaging of mammalian cells and the pathophysiology of H. pylori. 相似文献
106.
107.
Early‐shared Mycobacterium bovis bacillus Calmette–Guérin sub‐strains induce Th1 cytokine production in vivo
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Keiichi Taniguchi Yuuji Miyatake Daisuke Hayashi Atsuro Takami Saotomo Itoh Saburo Yamamoto Shigeaki Hida Kikuo Onozaki Takemasa Takii 《Microbiology and immunology》2015,59(11):684-689
108.
Yang Y Kurokawa T Takahama Y Nindita Y Mochizuki S Arakawa K Endo S Kinashi H 《Bioscience, biotechnology, and biochemistry》2011,75(6):1147-1153
The 113,463-bp nucleotide sequence of the linear plasmid pSLA2-M of Streptomyces rochei 7434AN4 was determined. pSLA2-M had a 69.7% overall GC content, 352-bp terminal inverted repeats with 91% (321/352) identity at both ends, and 121 open reading frames. The rightmost 14.6-kb sequence was almost (14,550/14,555) identical to that of the coexisting 211-kb linear plasmid pSLA2-L. Adjacent to this homologous region an 11.8-kb CRISPR cluster was identified, which is known to function against phage infection in prokaryotes. This cluster region as well as another one containing two large membrane protein genes (orf78 and orf79) were flanked by direct repeats of 194 and 566 bp respectively. Hence the insertion of circular DNAs containing each cluster by homologous recombination was suggested. In addition, the orf71 encoded a Ku70/Ku80-like protein, known to function in the repair of double-strand DNA breaks in eukaryotes, but disruption of it did not affect the radiation sensitivity of the mutant. A pair of replication initiation genes (orf1-orf2) were identified at the extreme left end. Thus, pSLA2-M proved to be a composite linear plasmid characterized by self-defense genes and homology with pSLA2-L that might have been generated by multiple recombination events. 相似文献
109.
Kitamura N Nakamura Y Miyamoto Y Miyamoto T Kabu K Yoshida M Futamura M Ichinose S Arakawa H 《PloS one》2011,6(1):e16060
Maintenance of healthy mitochondria prevents aging, cancer, and a variety of degenerative diseases that are due to the result of defective mitochondrial quality control (MQC). Recently, we discovered a novel mechanism for MQC, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria). However, a large part of the mechanisms for MQC remains unknown. Here, we report additional mechanisms for Mieap-regulated MQC. Reactive oxygen species (ROS) scavengers completely inhibited MALM. A mitochondrial outer membrane protein NIX interacted with Mieap in a ROS-dependent manner via the BH3 domain of NIX and the coiled-coil domain of Mieap. Deficiency of NIX also completely impaired MALM. When MALM was inhibited, Mieap induced vacuole-like structures (designated as MIV for Mieap-induced vacuole), which engulfed and degraded the unhealthy mitochondria by accumulating lysosomes. The inactivation of p53 severely impaired both MALM and MIV generation, leading to accumulation of unhealthy mitochondria. These results suggest that (1) mitochondrial ROS and NIX are essential factors for MALM, (2) MIV is a novel mechanism for lysosomal degradation of mitochondria, and (3) the p53-Mieap pathway plays a pivotal role in MQC by repairing or eliminating unhealthy mitochondria via MALM or MIV generation, respectively. 相似文献
110.
Ueta K Ishihara T Matsumoto Y Oku A Nawano M Fujita T Saito A Arakawa K 《Life sciences》2005,76(23):2655-2668
We examined the effects of T-1095, an orally active inhibitor of Na(+)-glucose cotransporter (SGLT), on the development and severity of diabetes in Goto-Kakizaki (GK) rat, a spontaneous, non-obese model of type 2 diabetes. T-1095 was administered as dietary admixture (0.1% w/w) beginning at 7 weeks of age for 32 weeks. Untreated male GK rats were hyperglycemic compared with Wistar rats. Throughout the study, T-1095 treatment significantly decreased both blood glucose and hemoglobin A(1C) levels in the GK rats. The concomitant increase of urinary glucose excretion indicated that the hypoglycemic action of T-1095 is derived from the enhancement of urinary glucose disposal. Although food intake was not changed in the T-1095-treated rats, the body weight gain was retarded. T-1095 treatment partially ameliorated oral glucose tolerance but not the impaired glucose-induced insulin secretion. Homeostasis model assessment (HOMA) indicated the existence of insulin resistance in GK rats and a significant restoration by T-1095-treatment. There was a reduction of the thermal response in tail-flick testing following long-term hyperglycemia (diabetic neuropathy). Treatment of T-1095 significantly prevented the development of diabetic neuropathy in male GK rats. Sustained improvement of hyperglycemia and prevention of diabetic neuropathy by the T-1095-treatment provide further support the use of SGLT inhibitors for the treatment of diabetes. 相似文献