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71.
Ruban AV Berera R Ilioaia C van Stokkum IH Kennis JT Pascal AA van Amerongen H Robert B Horton P van Grondelle R 《Nature》2007,450(7169):575-578
Under conditions of excess sunlight the efficient light-harvesting antenna found in the chloroplast membranes of plants is rapidly and reversibly switched into a photoprotected quenched state in which potentially harmful absorbed energy is dissipated as heat, a process measured as the non-photochemical quenching of chlorophyll fluorescence or qE. Although the biological significance of qE is established, the molecular mechanisms involved are not. LHCII, the main light-harvesting complex, has an inbuilt capability to undergo transformation into a dissipative state by conformational change and it was suggested that this provides a molecular basis for qE, but it is not known if such events occur in vivo or how energy is dissipated in this state. The transition into the dissipative state is associated with a twist in the configuration of the LHCII-bound carotenoid neoxanthin, identified using resonance Raman spectroscopy. Applying this technique to study isolated chloroplasts and whole leaves, we show here that the same change in neoxanthin configuration occurs in vivo, to an extent consistent with the magnitude of energy dissipation. Femtosecond transient absorption spectroscopy, performed on purified LHCII in the dissipative state, shows that energy is transferred from chlorophyll a to a low-lying carotenoid excited state, identified as one of the two luteins (lutein 1) in LHCII. Hence, it is experimentally demonstrated that a change in conformation of LHCII occurs in vivo, which opens a channel for energy dissipation by transfer to a bound carotenoid. We suggest that this is the principal mechanism of photoprotection. 相似文献
72.
Quesada V Conde L Villamor N Ordóñez GR Jares P Bassaganyas L Ramsay AJ Beà S Pinyol M Martínez-Trillos A López-Guerra M Colomer D Navarro A Baumann T Aymerich M Rozman M Delgado J Giné E Hernández JM González-Díaz M Puente DA Velasco G Freije JM Tubío JM Royo R Gelpí JL Orozco M Pisano DG Zamora J Vázquez M Valencia A Himmelbauer H Bayés M Heath S Gut M Gut I Estivill X López-Guillermo A Puente XS Campo E López-Otín C 《Nature genetics》2012,44(1):47-52
Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies. 相似文献
73.
Jaeschke H Kleinau G Sontheimer J Mueller S Krause G Paschke R 《Cellular and molecular life sciences : CMLS》2008,65(24):4028-4038
The majority of constitutively activating mutations (CAMs) of the thyroid-stimulating hormone receptor display a partially
activated receptor. Thus, full receptor activation requires a multiplex activation process. To define impacts of different
transmembrane helices (TMHs) on cooperative signal transduction, we combined single CAMs in particular TMHs to double mutations
and measured second messenger accumulation of the Gαs and the Gαq pathway. We observed a synergistic increase for basal activity of the Gαs pathway, for all characterized double mutants except for two combinations. Each double mutation, containing CAMs in TMH2,
6 and 7 showed the highest constitutive activities, suggesting that these helices contribute most to Gαs-mediated signaling. No single CAM revealed constitutive activity for the Gαq pathway. The double mutations with CAMs from TMH1, 2, 3 and 6 also exhibited increase for basal Gαq signaling. Our results suggest that TMH2, 6, 7 show selective preferences towards Gαs signaling, and TMH1, 2, 3, 6 for Gαq signaling. 相似文献
74.
STAR Consortium Saar K Beck A Bihoreau MT Birney E Brocklebank D Chen Y Cuppen E Demonchy S Dopazo J Flicek P Foglio M Fujiyama A Gut IG Gauguier D Guigo R Guryev V Heinig M Hummel O Jahn N Klages S Kren V Kube M Kuhl H Kuramoto T Kuroki Y Lechner D Lee YA Lopez-Bigas N Lathrop GM Mashimo T Medina I Mott R Patone G Perrier-Cornet JA Platzer M Pravenec M Reinhardt R Sakaki Y Schilhabel M Schulz H Serikawa T Shikhagaie M Tatsumoto S Taudien S Toyoda A Voigt B Zelenika D Zimdahl H Hubner N 《Nature genetics》2008,40(5):560-566
The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies. 相似文献
75.
Sandilands A Terron-Kwiatkowski A Hull PR O'Regan GM Clayton TH Watson RM Carrick T Evans AT Liao H Zhao Y Campbell LE Schmuth M Gruber R Janecke AR Elias PM van Steensel MA Nagtzaam I van Geel M Steijlen PM Munro CS Bradley DG Palmer CN Smith FJ McLean WH Irvine AD 《Nature genetics》2007,39(5):650-654
We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles. 相似文献
76.
A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15
Menzel S Garner C Gut I Matsuda F Yamaguchi M Heath S Foglio M Zelenika D Boland A Rooks H Best S Spector TD Farrall M Lathrop M Thein SL 《Nature genetics》2007,39(10):1197-1199
F cells measure the presence of fetal hemoglobin, a heritable quantitative trait in adults that accounts for substantial phenotypic diversity of sickle cell disease and beta thalassemia. We applied a genome-wide association mapping strategy to individuals with contrasting extreme trait values and mapped a new F cell quantitative trait locus to BCL11A, which encodes a zinc-finger protein, on chromosome 2p15. The 2p15 BCL11A quantitative trait locus accounts for 15.1% of the trait variance. 相似文献
77.
Jo-Anne Chan Katherine B. Howell Christine Langer Alexander G. Maier Wina Hasang Stephen J. Rogerson Michaela Petter Joanne Chesson Danielle I. Stanisic Michael F. Duffy Brian M. Cooke Peter M. Siba Ivo Mueller Peter C. Bull Kevin Marsh Freya J.I. Fowkes James G. Beeson 《Cellular and molecular life sciences : CMLS》2016,73(21):4141-4158
78.
79.
Simone Braig Daniel W. Mueller Tanja Rothhammer Anja-Katrin Bosserhoff 《Cellular and molecular life sciences : CMLS》2010,67(20):3535-3548
Since bone morphogenetic proteins (BMPs) play an important role in melanoma progression, we aimed to determine the molecular
mechanisms leading to overexpression of BMP4 in melanoma cells compared to normal melanocytes. With our experimental approach
we revealed that loss of expression of a microRNA represents the starting point for a signaling cascade finally resulting
in overexpression of BMP4 in melanoma cells. In detail, strongly reduced expression of the microRNA miR-196a in melanoma cells
compared to healthy melanocytes leads to enhanced HOX-B7 mRNA and protein levels, which subsequently raise Ets-1 activity
by inducing basic fibroblast growth factor (bFGF). Ets-1 finally accounts for induction of BMP4 expression. We were furthermore
able to demonstrate that bFGF-mediated induction of migration is achieved via activation of BMP4, thus determining BMP4 as
major modulator of migration in melanoma. In summary, our study provides insights into the early steps of melanoma progression
and might thereby harbor therapeutic relevance. 相似文献
80.