全文获取类型
收费全文 | 466篇 |
免费 | 24篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 5篇 |
2016年 | 8篇 |
2015年 | 18篇 |
2014年 | 20篇 |
2013年 | 36篇 |
2012年 | 26篇 |
2011年 | 26篇 |
2010年 | 20篇 |
2009年 | 16篇 |
2008年 | 24篇 |
2007年 | 34篇 |
2006年 | 17篇 |
2005年 | 35篇 |
2004年 | 34篇 |
2003年 | 29篇 |
2002年 | 36篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 12篇 |
1997年 | 8篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有490条查询结果,搜索用时 15 毫秒
91.
Kazumi Kajiwara Kentaro Watanabe Rei Tokiwa Tomoko Kurose Hiroaki Ohno Hiroko Tsutsumi Yoji Hata Kazuki Izumi Eiichi Kodama Masao Matsuoka Shinya Oishi Nobutaka Fujii 《Bioorganic & medicinal chemistry》2009,17(23):7964-7970
The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology. 相似文献
92.
Ken Horii Takashi Adachi Tetsuya Matsuda Tsutomu Tanaka Hiroshi Sahara Seiji Shibasaki Chiaki Ogino Yoji Hata Mitsuyoshi Ueda Akihiko Kondo 《Journal of Molecular Catalysis .B, Enzymatic》2009,59(4):297-301
β-Glucosidase (BGL1) from Aspergillus oryzae was efficiently produced in recombinant A. oryzae using sodM promoter-mediated expression system. The yield of BGL1 was 960 mg/l in liquid culture, which is 20-fold higher than the yield of BGL1 produced using the yeast Saccharomyces cerevisiae. Recombinant BGL1 converted isoflavone glycosides into isoflavone aglycones more efficiently than β-glucosidase from almond. In addition, BGL1 produced isoflavone aglycones even in the presence of the insoluble form of isoflavone glycosides. 相似文献
93.
Koichiro Higasa Yoji Kukita Kiyoko Kato Norio Wake Tomoko Tahira Kenshi Hayashi 《PLoS genetics》2009,5(5)
The haplotype map constructed by the HapMap Project is a valuable resource in the genetic studies of disease genes, population structure, and evolution. In the Project, Caucasian and African haplotypes are fairly accurately inferred, based mainly on the rules of Mendelian inheritance using the genotypes of trios. However, the Asian haplotypes are inferred from the genotypes of unrelated individuals based on population genetics, and are less accurate. Thus, the effects of this inaccuracy on downstream analyses needs to be assessed. We determined true Japanese haplotypes by genotyping 100 complete hydatidiform moles (CHM), each carrying a genome derived from a single sperm, using Affymetrix 500 K Arrays. We then assessed how inferred haplotypes can differ from true haplotypes, by phasing pseudo-individualized true haplotypes using the programs PHASE, fastPHASE, and Beagle. We found that, at various genomic regions, especially the MHC locus, the expansion of extended haplotype homozygosity (EHH), which is a measure of positive selection, is obscured when inferred Asian haplotype data is used to detect the expansion. We then mapped the genome using a new statistic, XDiHH, which directly detects the difference between the true and inferred haplotypes, in the determination of EHH expansion. We also show that the true haplotype data presented here is useful to assess and improve the accuracy of phasing of Asian genotypes. 相似文献
94.
Starting from (+)-epi- and (-)-vibo-quercitols readily produced by bioconversion of myo-inositol, some biologically interesting phosphate and polyphosphate analogues, including the Ins(1,4,5)P(3) derivatives of 3-deoxy- and 6-deoxy-D-myo-inositol, could be readily prepared in a conventional manner. In addition, chemical modification at C-2 of the 3-deoxy Ins(1,4,5)P(3) provided 2-epimer, and 2-deoxy and 2-deoxy-2-fluoro forms. Eight polyphosphate analogues obtained were assayed for biological activity against PDH-Pase and PDH-K, and G6Pase, but none proved positive. 相似文献
95.
Asami Y Oishi J Kitazaki H Kamimoto J Kang JH Niidome T Mori T Katayama Y 《Analytical biochemistry》2011,(1):1628-49
Here we developed a simple set-and-mix assay to perform high-throughput screening of protein kinase A (PKA) inhibitors from the LOPAC 1280 compound library. This assay is based on the color change of gold nanoparticles on aggregation induced by a cationic substrate peptide as coagulant. In spite of the simplicity of this assay system, this assay can be applied to drug screening based on cellular kinases. We successfully found several highly active inhibitors, including compounds that have not been reported before. 相似文献
96.
Kitajima N Watanabe K Morimoto S Sato Y Kiyonaka S Hoshijima M Ikeda Y Nakaya M Ide T Mori Y Kurose H Nishida M 《Biochemical and biophysical research communications》2011,(1):108-113
Obesity-related metabolic abnormalities, including chronic inflammation and oxidative stress, increase the risk of colorectal cancer. Dysregulation of the renin–angiotensin system (RAS) also plays a critical role in obesity-related metabolic disorders and in several types of carcinogenesis. In the present study, we examined the effects of an angiotensin-converting enzyme (ACE) inhibitor and angiotensin-II type 1 receptor blocker (ARB), both of which inhibit the RAS, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given 4 weekly subcutaneous injections of AOM (15 mg/kg body weight), and then, they received drinking water containing captopril (ACE inhibitor, 5 mg/kg/day) or telmisartan (ARB, 5 mg/kg/day) for 7 weeks. At sacrifice, administration of either captopril or telmisartan significantly reduced the total number of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, compared to that observed in the control group. The expression levels of TNF-α mRNA in the colonic mucosa of AOM-treated db/db mice were decreased by captopril and telmisartan. Captopril lowered the expression levels of TNF-α, IL-1β, IL-6, and PAI-1 mRNAs, while telmisartan lowered the expression levels of COX-2, IL-1β, IL-6, and PAI-1 mRNAs in the white adipose tissues of these mice. In addition, these agents significantly reduced the levels of urinary 8-OHdG, a surrogate marker of oxidative damage to DNA, in the experimental mice. These findings suggested that both ACE inhibitor and ARB suppress chemically-induced colon carcinogenesis by attenuating chronic inflammation and reducing oxidative stress in obese mice. Therefore, targeting dysregulation of the RAS might be an effective strategy for chemoprevention of colorectal carcinogenesis in obese individuals. 相似文献
97.
Hang Qi Hiroshi Takano Yoji Kato Qian Wu Chiharu Ogata Beiwei Zhu Yoshiyuki Murata Yoshimasa Nakamura 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
Phloxine B (PhB; 2′,4′,5′,7′-tetrabromo-4,5,6,7-tetrachloro-fluorescein), an artificial xanthene colorant, has been used as a red coloring agent in drugs and cosmetics as well as foods in some countries. However, little effort has been devoted to the study of this colorant as a potentially useful medicinal agent.Methods
We investigated the daily light-induced photocytotoxicity of PhB in two human leukemia cells, HL-60 and Jurkat, and its underlying mechanisms by in vitro experiments using antioxidants.Reuslts and conclusions
PhB inhibited cell proliferation more preferentially to HL-60 cells than to Jurkat cells. Co-treatment of catalase completely blocked the photocytotoxicity by PhB in HL-60 cells, whereas the effect of histidine was only partial, suggesting that hydrogen peroxide (H2O2), rather than singlet oxygen, might be a prerequisite for the PhB-induced HL-60 cell death. Actually, PhB produced a significant amount of H2O2 in the media as well as in the cells in concentration- and light-dependent manners. Furthermore, methionine, a hypochlorous acid (HOCl) scavenger, also significantly attenuated the cytotoxicity in HL-60 cells, but not in Jurkat cells, indicating the involvement of myeloperoxidase (MPO)-dependent hypohalous acid formation during the photocytotoxicity. In vitro experiments revealed that halogenated tyrosine was generated from the reaction of bovine serum albumin with PhB and HL-60 cell lysate. The present findings suggested that PhB induced a differential photodynamic action in the MPO-containing leukemia cells through an H2O2-dependent mechanism.General significance
Our findings provide new insights into the molecular mechanisms underlying the PhB-induced apoptosis and also evaluated PhB as a promising PDT agent. 相似文献98.
Bando H Hisada H Ishida H Hata Y Katakura Y Kondo A 《Applied microbiology and biotechnology》2011,92(3):561-569
A novel promoter from a hemolysin-like protein encoding the gene, hlyA, was characterized for protein overexpression in Aspergillus oryzae grown in solid-state culture. Using endo-1,4-β-glucanase from A. oryzae (CelA) as the reporter, promoter activity was found to be higher than that of the α-amylase (amyA) and manganese superoxide dismutase (sodM) genes not only in wheat bran solid-state culture but also in liquid culture. Expression of the A. oryzae endoglucanase CelB and two heterologous endoglucanases (TrEglI and TrEglIII from Trichoderma reesei) under the control of the hlyA promoter were also found to be stronger than under the control of the amyA promoter in A. oryzae grown in wheat bran solid-state culture, suggesting that the hlyA promoter may be useful for the overproduction of other proteins as well. In wheat bran solid-state culture, the productivity
of the hlyA promoter in terms of protein produced was high when the cultivation temperature was 30°C or 37°C, when the water content
was 0.6 or 0.8 ml/g wheat bran, and from 48 to 72 h after inoculation. Because A. oryzae sporulated actively under these conditions and because hemolysin has been reported to play a role in fungal fruiting body
formation, high-level expression of hlyA may be related to sporulation. 相似文献
99.
Characteristic microbial community of a dry thermophilic methanogenic digester: its long-term stability and change with feeding 总被引:1,自引:0,他引:1
Tang YQ Ji P Hayashi J Koike Y Wu XL Kida K 《Applied microbiology and biotechnology》2011,91(5):1447-1461
Thermophilic dry anaerobic digestion of sludge for cellulose methanization was acclimated at 53 °C for nearly 5 years using
a waste paper-based medium. The stability of the microbial community structure and the microbial community responsible for
the cellulose methanization were studied by 16S rRNA gene-based clone library analysis. The microbial community structure
remained stable during the long-term acclimation period. Hydrogenotrophic methanogens dominated in methanogens and Methanothermobacter, Methanobacterium, Methanoculleus, and Methanosarcina were responsible for the methane production. Bacteria showed relatively high diversity and distributed mainly in the phyla
Firmicutes, Bacteroidetes, and Synergistetes. Ninety percent of operational taxonomic units (OTUs) were affiliated with the phylum Firmicutes, indicating the crucial roles of this phylum in the digestion. Relatives of Clostridium stercorarium, Clostridium thermocellum, and Halocella cellulosilytica were dominant cellulose degraders. The acclimated stable sludge was used to treat garbage stillage discharged from a fuel
ethanol production process, and the shift of microbial communities with the change of feed was analyzed. Both archaeal and
bacterial communities had obviously changed: Methanoculleus spp. and Methanothermobacter spp. and the protein- and fatty acid-degrading bacteria became dominant. Accumulation of ammonia as well as volatile fatty
acids led to the inhibition of microbial activity and finally resulted in the deterioration of methane fermentation of the
garbage stillage. 相似文献
100.