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1.
Hyperthermia is a potent radio enhancer. Studies using hypothermia in combination with irradiation have given confusing results due to lack of uniformity in experimental design. This report shows that hypothermia might have potential significance in the treatment of malignant cells with both thermo- and radiotherapy. Reuber H35 hepatoma cells, clone KRC-7 were used to study the effect of hypothermia on cell kinetics and subsequent response to hyperthermia and/or X rays. Cells were incubated at 8.5 degrees C or between 25 and 37 degrees C for 24 hr prior to hyperthermia or irradiation. Hypothermia caused sensitization to both hyperthermia and X rays. Maximum sensitization was observed between 25 and 30 degrees C and no sensitization was found at 8.5 degrees C. At 25 degrees C maximum sensitization was achieved in approximately 24 hr, cell proliferation was almost completely blocked, and cells gradually accumulated in the G2 phase of the cell cycle. In contrast to the effect of hypothermia on either hyperthermia or X rays alone, thermal radiosensitization was decreased in hypothermically pretreated cells (24 hr at 25 degrees C) compared to control cells (37 degrees C). The expression of thermotolerance and the rate of development at 37 degrees C after an initial heating at 42.5 degrees C were not influenced after preincubation at 25 degrees C for 24 hr. The expression of thermotolerance for heat or heat plus X rays during incubation at 41 degrees C occurred in a significantly smaller number of cells after 24 hr preincubation at 25 degrees C. The enhanced thermo- and radiosensitivity in hypothermically treated cells disappeared in approximately 6 hr after return to 37 degrees C. 相似文献
2.
Mike F. Müller Simone Florian Stefanie Pommer Martin Osterhoff R. Steven Esworthy Fong-Fong Chu Regina Brigelius-Flohé Anna P. Kipp 《PloS one》2013,8(8)
The selenoprotein glutathione peroxidase-2 (GPx2) appears to have a dual role in carcinogenesis. While it protected mice from colon cancer in a model of inflammation-triggered carcinogenesis (azoxymethane and dextran sodium sulfate treatment), it promoted growth of xenografted tumor cells. Therefore, we analyzed the effect of GPx2 in a mouse model mimicking sporadic colorectal cancer (azoxymethane-treatment only). GPx2-knockout (KO) and wild-type (WT) mice were adjusted to an either marginally deficient (−Se), adequate (+Se), or supranutritional (++Se) selenium status and were treated six times with azoxymethane (AOM) to induce tumor development. In the −Se and ++Se groups, the number of tumors was significantly lower in GPx2-KO than in respective WT mice. On the +Se diet, the number of dysplastic crypts was reduced in GPx2-KO mice. This may be explained by more basal and AOM-induced apoptotic cell death in GPx2-KO mice that eliminates damaged or pre-malignant epithelial cells. In WT dysplastic crypts GPx2 was up-regulated in comparison to normal crypts which might be an attempt to suppress apoptosis. In contrast, in the +Se groups tumor numbers were similar in both genotypes but tumor size was larger in GPx2-KO mice. The latter was associated with an inflammatory and tumor-promoting environment as obvious from infiltrated inflammatory cells in the intestinal mucosa of GPx2-KO mice even without any treatment and characterized as low-grade inflammation. In WT mice the number of tumors tended to be lowest in +Se compared to −Se and ++Se feeding indicating that selenium might delay tumorigenesis only in the adequate status. In conclusion, the role of GPx2 and presumably also of selenium depends on the cancer stage and obviously on the involvement of inflammation. 相似文献
3.
Zi-Feng Jiang Fangfang Xia Kipp W. Johnson Christopher D. Brown Elizabeth Bartom Jigyasa H. Tuteja Rick Stevens Robert L. Grossman Marina Brumin Kevin P. White Murad Ghanim 《Applied and environmental microbiology》2013,79(5):1757-1759
“Candidatus Portiera aleyrodidarum” is the primary endosymbiont of whiteflies. We report two complete genome sequences of this bacterium from the worldwide invasive B and Q biotypes of the whitefly Bemisia tabaci. Differences in the two genome sequences may add insights into the complex differences in the biology of both biotypes. 相似文献
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Different modes of sodium-D-glucose cotransporter-mediated D-glucose uptake regulation in Caco-2 cells 总被引:1,自引:0,他引:1
Khoursandi S Scharlau D Herter P Kuhnen C Martin D Kinne RK Kipp H 《American journal of physiology. Cell physiology》2004,287(4):C1041-C1047
We recently reported that a considerable amount of the sodium-D-glucose cotransporter SGLT1 present in Caco-2 cells, a model for human enterocytes, is located in intracellular compartments attached to microtubules (Kipp H, Khoursandi S, Scharlau D, and Kinne RKH. Am J Physiol Cell Physiol 285: C737C749, 2003). A similar distribution pattern was also observed in enterocytes in thin sections from human jejunum, highlighting the validity of the Caco-2 cell model. Fluorescent surface labeling of live Caco-2 cells revealed that the intracellular compartments containing SGLT1 were accessible by endocytosis. To elucidate the role of endosomal SGLT1 in the regulation of sodium-dependent D-glucose uptake into enterocytes, we compared SGLT1-mediated D-glucose uptake into Caco-2 cells with the subcellular distribution of SGLT1 after challenging the cells with different stimuli. Incubation (90 min) of Caco-2 cells with mastoparan (50 µM), a drug that enhances apical endocytosis, shifted a large amount of SGLT1 from the apical membrane to intracellular sites and significantly reduced sodium-dependent -[14C]methyl-D-glucose uptake (60%). We also investigated the effect of altered extracellular D-glucose levels. Cells preincubated (1 h) with D-glucose-free medium exhibited significantly higher sodium-dependent -[14C]methyl-D-glucose uptake (+45%) than did cells preincubated with high D-glucose medium (100 mM, 1 h). Interestingly, regulation of SGLT1-mediated D-glucose uptake into Caco-2 cells by extracellular D-glucose levels occurred without redistribution of cellular SGLT1. These data suggest that, pharmacologically, D-glucose uptake can be regulated by a shift of SGLT1 between the plasma membrane and the endosomal pool; however, regulation by the physiological substrate D-glucose can be explained only by an alternative mechanism. endosomes; enterocytes 相似文献
6.
Remko?de Knikker Youjun?Guo Jin-long?Li Albert?KH?Kwan Kevin?Y?Yip David?W?Cheung Kei-Hoi?CheungEmail author 《BMC bioinformatics》2004,5(1):25
Background
Very often genome-wide data analysis requires the interoperation of multiple databases and analytic tools. A large number of genome databases and bioinformatics applications are available through the web, but it is difficult to automate interoperation because: 1) the platforms on which the applications run are heterogeneous, 2) their web interface is not machine-friendly, 3) they use a non-standard format for data input and output, 4) they do not exploit standards to define application interface and message exchange, and 5) existing protocols for remote messaging are often not firewall-friendly. To overcome these issues, web services have emerged as a standard XML-based model for message exchange between heterogeneous applications. Web services engines have been developed to manage the configuration and execution of a web services workflow. 相似文献7.
Molecular targeting of inhibitor of apoptosis proteins based on small molecule mimics of natural binding partners 总被引:3,自引:0,他引:3
Kipp RA Case MA Wist AD Cresson CM Carrell M Griner E Wiita A Albiniak PA Chai J Shi Y Semmelhack MF McLendon GL 《Biochemistry》2002,41(23):7344-7349
An assay based on a solvent-sensitive fluorogenic dye molecule, badan, is used to test the binding affinity of a library of tetrapeptide molecules for the BIR3 (baculovirus IAP repeat) domain of XIAP (X-linked inhibitor of apoptosis protein). The fluorophore is attached to a tetrapeptide, Ala-Val-Pro-Cys-NH(2), through a thiol linkage and, upon binding to XIAP, undergoes a solvatochromic shift in fluorescence emission. When a molecule (e.g., a natural protein known to bind to XIAP or a tetrapeptide mimic) displaces the dye, the emission shifts back to the spectrum observed in water. As emission intensity is related to the binding of the tetrapeptide, the intensity can be used to determine the equilibrium constant, K, for the displacement of the dye by the tetrapeptide. The results permit residue-specific analysis of the interaction. Furthermore, we show that hydrophobic effects in the fourth position are general and can effectively increase overall affinity. 相似文献
8.
Newly synthesized canalicular ectoenzymes and a cell adhesion molecule (cCAM105) have been shown to traffic from the Golgi to the basolateral plasma membrane, from where they transcytose to the apical bile canalicular domain. It has been proposed that all canalicular proteins are targeted via this indirect route in hepatocytes. We studied the membrane targeting of rat canalicular proteins by in vivo [(35)S]methionine metabolic labeling followed by preparation of highly purified Golgi membranes and canalicular (CMVs) and sinusoidal/basolateral (SMVs) membrane vesicles and subsequent immunoprecipitation. In particular, we compared membrane targeting of newly synthesized canalicular ABC (ATP-binding cassette) transporters MDR1, MDR2, and SPGP (sister of P-glycoprotein) with that of cCAM105. Significant differences were observed in metabolic pulse-chase labeling experiments with regard to membrane targeting of these apical proteins. After a chase time of 15 min, cCAM105 appeared exclusively in SMVs, peaked at 1 h, and progressively declined thereafter. In CMVs, cCAM105 was first detected after 1 h and subsequently increased for 3 h. This findings confirm the transcytotic targeting of cCAM105 reported in earlier studies. In contrast, at no time point investigated were MDR1, MDR2, and SPGP detected in SMVs. In CMVs, MDR1 and MDR2 appeared after 30 min, whereas SPGP appeared after 2 h of labeling. In Golgi membranes, each of the ABC transporters peaked at 30 min and was virtually absent thereafter. These data suggest rapid, direct targeting of newly synthesized MDR1 and MDR2 from the Golgi to the bile canaliculus and transient sequestering of SPGP in an intracellular pool en route from the Golgi to the apical plasma membrane. This study provides biochemical evidence for direct targeting of newly synthesized apical ABC transporters from the Golgi to the bile canaliculus in vivo. 相似文献
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