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41.
Radoshitzky SR Abraham J Spiropoulou CF Kuhn JH Nguyen D Li W Nagel J Schmidt PJ Nunberg JH Andrews NC Farzan M Choe H 《Nature》2007,446(7131):92-96
At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use alpha-dystroglycan. Here we show a specific, high-affinity association between transferrin receptor 1 (TfR1) and the entry glycoprotein (GP) of Machupo virus. Expression of human TfR1, but not human transferrin receptor 2, in hamster cell lines markedly enhanced the infection of viruses pseudotyped with the GP of Machupo, Guanarito and Junin viruses, but not with those of Lassa or lymphocytic choriomeningitis viruses. An anti-TfR1 antibody efficiently inhibited the replication of Machupo, Guanarito, Junin and Sabia viruses, but not that of Lassa virus. Iron depletion of culture medium enhanced, and iron supplementation decreased, the efficiency of infection by Junin and Machupo but not Lassa pseudoviruses. These data indicate that TfR1 is a cellular receptor for New World haemorrhagic fever arenaviruses. 相似文献
42.
RA Scott V Lagou RP Welch E Wheeler ME Montasser J Luan R Mägi RJ Strawbridge E Rehnberg S Gustafsson S Kanoni LJ Rasmussen-Torvik L Yengo C Lecoeur D Shungin S Sanna C Sidore PC Johnson JW Jukema T Johnson A Mahajan N Verweij G Thorleifsson JJ Hottenga S Shah AV Smith B Sennblad C Gieger P Salo M Perola NJ Timpson DM Evans BS Pourcain Y Wu JS Andrews J Hui LF Bielak W Zhao M Horikoshi P Navarro A Isaacs JR O'Connell K Stirrups V Vitart C Hayward T Esko E Mihailov RM Fraser T Fall BF Voight 《Nature genetics》2012,44(9):991-1005
Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. 相似文献
43.
Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice 总被引:2,自引:0,他引:2
Wang F Paradkar PN Custodio AO McVey Ward D Fleming MD Campagna D Roberts KA Boyartchuk V Dietrich WF Kaplan J Andrews NC 《Nature genetics》2007,39(8):1025-1032
We undertook a quantitative trait locus (QTL) analysis in mice to identify modifier genes that might influence the severity of human iron disorders. We identified a strong QTL on mouse chromosome 9 that differentially affected macrophage iron burden in C57BL/10J and SWR/J mice. A C57BL/10J missense allele of an evolutionarily conserved gene, Mon1a, cosegregated with the QTL in congenic mouse lines. We present evidence that Mon1a is involved in trafficking of ferroportin, the major mammalian iron exporter, to the surface of iron-recycling macrophages. Differences in amounts of surface ferroportin correlate with differences in cellular iron content. Mon1a is also important for trafficking of cell-surface and secreted molecules unrelated to iron metabolism, suggesting that it has a fundamental role in the mammalian secretory apparatus. 相似文献
44.
Gregory SG Barlow KF McLay KE Kaul R Swarbreck D Dunham A Scott CE Howe KL Woodfine K Spencer CC Jones MC Gillson C Searle S Zhou Y Kokocinski F McDonald L Evans R Phillips K Atkinson A Cooper R Jones C Hall RE Andrews TD Lloyd C Ainscough R Almeida JP Ambrose KD Anderson F Andrew RW Ashwell RI Aubin K Babbage AK Bagguley CL Bailey J Beasley H Bethel G Bird CP Bray-Allen S Brown JY Brown AJ Buckley D Burton J Bye J Carder C Chapman JC Clark SY Clarke G Clee C Cobley V Collier RE Corby N 《Nature》2006,441(7091):315-321
The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome. 相似文献
45.
The developmental transcriptome of Drosophila melanogaster 总被引:2,自引:0,他引:2
Graveley BR Brooks AN Carlson JW Duff MO Landolin JM Yang L Artieri CG van Baren MJ Boley N Booth BW Brown JB Cherbas L Davis CA Dobin A Li R Lin W Malone JH Mattiuzzo NR Miller D Sturgill D Tuch BB Zaleski C Zhang D Blanchette M Dudoit S Eads B Green RE Hammonds A Jiang L Kapranov P Langton L Perrimon N Sandler JE Wan KH Willingham A Zhang Y Zou Y Andrews J Bickel PJ Brenner SE Brent MR Cherbas P Gingeras TR Hoskins RA Kaufman TC Oliver B Celniker SE 《Nature》2011,471(7339):473-479
46.
Pinus aristata Engelm. forest vegetation in Colorado was studied to determine vegetation composition and the relationship between vegetation and environment. Species percent cover, tree size class, and environmental variables were recorded for 49 plots. Previously collected data for 4 plots form New Mexico were included. Environmental variables included latitude, longitude, elevation, slope, aspect, topographic position, parent material, percent rock cover, mean rock size, litter depth, estimated plot age class, and evidence of anthropogenic disturbance. Soils were analyzed for texture, depth, and percent carbon and nitrogen. Pinus aristata foliage was analyzed for percent nitrogen and phosphorus. Direct and indirect gradient analyses (CANOCO) were used to determine environmental factors associated with community composition. Vegetation in P. aristata forests is influenced primarily by elevation and soil pH. Substrate, soil texture, topographic position, and geographic location are secondary factors. Six plant associations were identified using cluster analysis (listed in an elevational sequence from low to high): Pinus aristata/ Festuca arizonica Vasey, Pinus aristata / Festuca thurberi Vasey, Pinus aristata / Juniperus communis L., Pinus aristata / Vaccinium myrtilus L., Pinus aristata / Ribes montigenum McClatchie, and Pinus aristata / Trifolium dasyphyllum Torr. & Gray. 相似文献
47.
48.
Henriikka Kentala Annika Koponen Helena Vihinen Juho Pirhonen Gerhard Liebisch Zoltan Pataj Annukka Kivelä Shiqian Li Leena Karhinen Eeva Jääskeläinen Robert Andrews Leena Meriläinen Silke Matysik Elina Ikonen You Zhou Eija Jokitalo Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2018,75(21):4041-4057
ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in endoplasmic reticulum (ER)—lipid droplet (LD) contacts, triacylglycerol (TG) metabolism, cholesterol transport, adrenocortical steroidogenesis, and actin-dependent cell dynamics. Here, we characterize the role of ORP2 in carbohydrate and lipid metabolism by employing ORP2-knockout (KO) hepatoma cells (HuH7) generated by CRISPR-Cas9 gene editing. The ORP2-KO and control HuH7 cells were subjected to RNA sequencing, analyses of Akt signaling, carbohydrate and TG metabolism, the extracellular acidification rate, and the lipidome, as well as to transmission electron microscopy. The loss of ORP2 resulted in a marked reduction of active phosphorylated Akt(Ser473) and its target Glycogen synthase kinase 3β(Ser9), consistent with defective Akt signaling. ORP2 was found to form a physical complex with the key controllers of Akt activity, Cdc37, and Hsp90, and to co-localize with Cdc37 and active Akt(Ser473) at lamellipodial plasma membrane regions, in addition to the previously reported ER–LD localization. ORP2-KO reduced glucose uptake, glycogen synthesis, glycolysis, mRNA-encoding glycolytic enzymes, and SREBP-1 target gene expression, and led to defective TG synthesis and storage. ORP2-KO did not reduce but rather increased ER–LD contacts under basal culture conditions and interfered with their expansion upon fatty acid loading. Together with our recently published work (Kentala et al. in FASEB J 32:1281–1295, 2018), this study identifies ORP2 as a new regulatory nexus of Akt signaling, cellular energy metabolism, actin cytoskeletal function, cell migration, and proliferation. 相似文献
49.
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project 总被引:2,自引:0,他引:2
ENCODE Project Consortium Birney E Stamatoyannopoulos JA Dutta A Guigó R Gingeras TR Margulies EH Weng Z Snyder M Dermitzakis ET Thurman RE Kuehn MS Taylor CM Neph S Koch CM Asthana S Malhotra A Adzhubei I Greenbaum JA Andrews RM Flicek P Boyle PJ Cao H Carter NP Clelland GK Davis S Day N Dhami P Dillon SC Dorschner MO Fiegler H Giresi PG Goldy J Hawrylycz M Haydock A Humbert R James KD Johnson BE Johnson EM Frum TT Rosenzweig ER Karnani N Lee K Lefebvre GC Navas PA Neri F Parker SC Sabo PJ 《Nature》2007,447(7146):799-816