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71.
Biosynthesis and secretion of salusin-alpha from human cells 总被引:1,自引:0,他引:1
Salusins originally identified using bioinformatics analyses have been shown to act on the cardiovascular and endocrine systems. Although the hypotensive activity of salusin-alpha is limited, it exerts a significant anti-atherosclerotic effect via suppression of foam cell formation in human monocyte-derived macrophages by down-regulating acyl-CoA:cholesterol acyltransferase-1. Furthermore, serum salusin-alpha levels show a close negative correlation with the severity of atherosclerotic diseases. However, biosynthesis and secretion of salusin-alpha peptide from cultured mammalian cells have not been demonstrated to date. We examined the expression, synthesis and release of salusin-alpha in human-derived cell lines. Preprosalusin mRNA and protein were detected ubiquitously in all cells tested, whereas the processing of preprosalusin into salusin-alpha peptide is dependent upon each cell type. Immunohistochemical study revealed the most abundant salusin-alpha-like immunoreactivity to be present in HeLa cells which released salusin-alpha-like immunoreactivity into the culture supernatant. Analysis of extracted conditioned media from HeLa cells by reverse-phase high performance liquid chromatography coupled with radioimmunoassay detection revealed a single immunoreactive component that co-eluted with authentic salusin-alpha. These results present the first evidence that salusin-alpha is biosynthesized and released from human-derived cells. 相似文献
72.
We reported previously that Coprinus cinereus Lim15/Dmc1 (CcLim15), a meiosis-specific recA-like protein, could specifically activate C. cinereus DNA topoisomerase II (CcTopII). In particular, it enhanced the catenation activity of CcTopII in vitro at the meiotic prophase
stage (Iwabata K, Koshiyama A, Yamaguchi T, Sugawara H, Hamada NF, Namekawa HS, Ishii S, Ishizaki T, Chiku H, Nara T, Sakaguchi
K, Nucleic Acids Res, 33:5809–5818, 2005). In this study, the interaction between CcTopII and CcLim15, especially during catenation,
was investigated in detail using atomic force microscopy. We demonstrated earlier that CcLim15 enhanced the catenation activity
of CcTopII in a dose-dependent manner. When using two different-sized plasmid rings (5.4 and 3 kbp), which did not have any
homologous sequence regions, equal proportions of homologous and heterologous catenanes were produced, suggesting that CcLim15
causes an increase in catenation activity irrespective of the presence of homologous sequences between the rings. We also
showed that CcLim15 works as a DNA-condensing agent. Therefore, we speculate that CcLim15 may work as a DNA-condensing factor
specific to the zygotene event and that CcTopII is likely to resolve tangles when the chromosomes initiate pairing at multiple
sites by CcLim15. 相似文献
73.
74.
Yoshiyuki Mizushina Toshifumi Takeuchi Yoichi Takakusagi Yuko Yonezawa Takeshi Mizuno Ken-ichiro Yanagi Naoko Imamoto Fumio Sugawara Kengo Sakaguchi Hiromi Yoshida Masatoshi Fujita 《Biochimica et Biophysica Acta (BBA)/General Subjects》2008
A human replication initiation protein Cdt1 is a very central player in the cell cycle regulation of DNA replication, and geminin down-regulates Cdt1 function by directly binding to it. It has been demonstrated that Cdt1 hyperfunction resulting from Cdt1–geminin imbalance, for example by geminin silencing with siRNA, induces DNA re-replication and eventual cell death in some cancer-derived cell lines. In the present study, we first established a high throughput screening system based on modified ELISA (enzyme linked immunosorbent assay) to identify compounds that interfere with human Cdt1–geminin binding. Using this system, we found that coenzyme Q10 (CoQ10) can inhibit Cdt1–geminin interaction in vitro. CoQ compound is an isoprenoid quinine that functions as an electron carrier in the mitochondrial respiratory chain in eukaryotes. CoQ10, having a longer isoprenoid chain, was the strongest inhibitor of Cdt1–geminin binding in the tested CoQs, with 50% inhibition observed at concentrations of 16.2 μM. Surface plasmon resonance analysis demonstrated that CoQ10 bound selectively to Cdt1, but did not interact with geminin. Moreover, CoQ10 had no influence on the interaction between Cdt1 and mini-chromosome maintenance (MCM)4/6/7 complexes. These results suggested that CoQ10 inhibits Cdt1–geminin complex formation by binding to Cdt1 and thereby could liberate Cdt1 from inhibition by geminin. Using three-dimensional computer modeling analysis, CoQ10 was considered to interact with the geminin interaction interface on Cdt1, and was assumed to make hydrogen bonds with the residue of Arg243 of Cdt1. CoQ10 could prevent the growth of human cancer cells, although only at high concentrations, and it remains unclear whether such an inhibitory effect is associated with the interference with Cdt1–geminin binding. The application of inhibitors for the formation of Cdt1–geminin complex is discussed. 相似文献
75.
Plant DNA polymerase lambda, a DNA repair enzyme that functions in plant meristematic and meiotic tissues. 总被引:2,自引:0,他引:2
Yukinobu Uchiyama Seisuke Kimura Taichi Yamamoto Toyotaka Ishibashi Kengo Sakaguchi 《European journal of biochemistry》2004,271(13):2799-2807
Little is known about the functions of DNA polymerase lambda (Pol lambda) recently identified in mammals. From the genomic sequence information of rice and Arabidopsis, we found that Pol lambda may be the only member of the X-family in higher plants. We have succeeded in isolating the cDNA and recombinant protein of Pol lambda in a higher plant, rice (Oryza sativa L. cv. Nipponbare) (OsPol lambda). OsPol lambda had activities of DNA polymerase, terminal deoxyribonucleotidyl transferase and deoxyribose phosphate lyase, a marker enzyme for base excision repair. It also interacted with rice proliferating cell nuclear antigen (OsPCNA) in a pull-down assay. OsPCNA increased the processivity of OsPol lambda. Northern blot analysis showed that the level of OsPol lambda expression correlated with cell proliferation in meristematic and meiotic tissues, and was induced by DNA-damaging treatments. These properties suggest that plant Pol lambda is a DNA repair enzyme which functions in plant meristematic and meiotic tissues, and that it can substitute for Pol beta and terminal deoxyribonucleotidyl transferase. 相似文献
76.
Takehara M Ino K Takakusagi Y Oshikane H Nureki O Ebina T Mizukami F Sakaguchi K 《Analytical biochemistry》2008,373(2):322-329
Two kinds of layer silicate powder, Micromica and chlorite, were used to aid protein crystallization by the addition to hanging drops. Using appropriate crystallization buffers, Micromica powder facilitated crystal growth speed for most proteins tested in this study. Furthermore, the addition of Micromica powder to hanging drops allowed the successful crystallization of lysozyme, catalase, concanavalin A, and trypsin even at low protein concentrations and under buffer conditions that otherwise would not generate protein crystals. Except for threonine synthase and apoferritin, the presence of chlorite delayed crystallization but induced the formation of large crystals. X-ray analysis of thaumatin crystals generated by our novel procedure gave better quality data than did that of crystals obtained by a conventional hanging drop method. Our results suggest that the speed of crystal growth and the quality of the corresponding X-ray data may be inversely related, at least for the formation of thaumatin crystals. The effect of Micromica and chlorite powders and the application of layer silicate powder for protein crystallization are discussed. 相似文献
77.
78.
Ryuji Tsunekawa Kengo Hanaya Shuhei Higashibayashi 《Bioscience, biotechnology, and biochemistry》2018,82(8):1316-1322
Fisetin and 2′,4′,6′-trihydroxydihyrochalcone 4′-O-β-neohesperidoside were synthesized from commercially available quercetin and naringin in five steps. The key steps are site-selective deacetylation and subsequent deoxygenation. The target molecules were obtained in 37% and 23% yields from the starting materials, respectively. 相似文献
79.
Takeshi Fukuda Takashi Ishiyama Takahiro Katagiri Kenjiro Ueda Sumie Muramatsu Masami Hashimoto Anri Aki Daichi Baba Kengo Watanabe Naoki Tanaka 《Bioorganic & medicinal chemistry letters》2018,28(20):3333-3337
Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis. The inhibition of hepcidin may be a favorable strategy for the treatment of anemia of chronic disease. Here, we have reported the design, synthesis, and structure–activity relationships (SAR) of a series of 4-aminopyrimidine compounds as inhibitors of hepcidin production. The optimization study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a mouse model of interleukin-6-induced acute inflammation. 相似文献
80.
Cloning and Functional Expression of a Novel Geranylgeranyl Pyrophosphate Synthase Gene from Arabidopsis thaliana in Escherichia coli 总被引:1,自引:0,他引:1
Zhu Fen; Suzuki Kengo; Okada Kazunori; Tanaka Katsunori; Nakagawa Tsuyoshi; Kawamukai Makoto; Matsuda Hideyuki 《Plant & cell physiology》1997,38(3):357-361
A gene encoding a novel geranylgeranyl pyrophosphate (GGPP)synthase from Arabidopsis thaliana has been identified and termedGGPS5. The gene has been sequenced and expressed in Escherichiacoli. The deduced amino acid sequence showed 64.5% and 57.5%identity with a putative GGPP synthase from Arabidopsis andCapsicum annuum, respectively. GGPP enzymatic activity was detectedin E. coli cells expressing the GGPS5 gene in two differentways. One was the direct measurement of GGPP synthase activityin cell extracts and the other was the yellow color productionof cells when the GGPS5 gene was co-expressed with crtB, crtI,crtX, crtY and crtZ genes derived from Erwinia uredovora. (Received May 20, 1996; Accepted December 14, 1996) 相似文献