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41.
Topoisomerase IIIalpha is required for normal proliferation and telomere stability in alternative lengthening of telomeres
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Temime-Smaali N Guittat L Wenner T Bayart E Douarre C Gomez D Giraud-Panis MJ Londono-Vallejo A Gilson E Amor-Guéret M Riou JF 《The EMBO journal》2008,27(10):1513-1524
Topoisomerase (Topo) IIIalpha associates with BLM helicase, which is proposed to be important in the alternative lengthening of telomeres (ALT) pathway that allows telomere recombination in the absence of telomerase. Here, we show that human Topo IIIalpha colocalizes with telomeric proteins at ALT-associated promyelocytic bodies from ALT cells. In these cells, Topo IIIalpha immunoprecipitated with telomere binding protein (TRF) 2 and BLM and was shown to be associated with telomeric DNA by chromatin immunoprecipitation, suggesting that these proteins form a complex at telomere sequences. Topo IIIalpha depletion by small interfering RNA reduced ALT cell survival, but did not affect telomerase-positive cell lines. Moreover, repression of Topo IIIalpha expression in ALT cells reduced the levels of TRF2 and BLM proteins, provoked a strong increase in the formation of anaphase bridges, induced the degradation of the G-overhang signal, and resulted in the appearance of DNA damage at telomeres. In contrast, telomere maintenance and TRF2 levels were unaffected in telomerase-positive cells. We conclude that Topo IIIalpha is an important telomere-associated factor, essential for telomere maintenance and chromosome stability in ALT cells, and speculate on its potential mechanistic function. 相似文献
42.
The recently identified RNF125 [RING (really interesting new gene) finger protein 125], or TRAC-1 (T-cell RING protein in activation 1), is unique among ubiquitin ligases in being a positive regulator of T-cell activation. In addition, TRAC-1 has been shown to down-modulate HIV replication and to inhibit pathogen-induced cytokine production. However, apart from the presence of an N-terminal C3HC4 (Cys(3)-His-Cys(4)) RING domain, the TRAC-1 protein remains uncharacterized. In the present paper, we report novel interactions and modifications for TRAC-1, and elucidate its domain organization. Specifically, we determine that TRAC-1 associates with membranes and is excluded from the nucleus through myristoylation. Our data are further consistent with a crucial role for the C-terminus in TRAC-1 function. In this region, novel domains were recognized through the identification of three closely related proteins: RNF114, RNF138 and RNF166. TRAC-1 and its relatives were found to contain, apart from the RING domain, a C2HC (Cys(2)-His-Cys)- and two C2H2 (Cys(2)-His(2))-type zinc fingers, as well as a UIM (ubiquitin-interacting motif). The UIM of TRAC-1 binds Lys(48)-linked polyubiquitin chains and is, together with the RING domain, required for auto-ubiquitination. As a consequence of auto-ubiquitination, the half-life of TRAC-1 is shorter than 30 min. The identification of these novel modifications, interactions, domains and relatives significantly widens the contexts for investigating TRAC-1 activity and regulation. 相似文献
43.
Pollen productivity estimates of key European plant taxa for quantitative reconstruction of past vegetation: a review 总被引:2,自引:2,他引:0
Anna Broström Anne Birgitte Nielsen Marie-José Gaillard Kari Hjelle Florence Mazier Heather Binney Jane Bunting Ralph Fyfe Viveca Meltsov Anneli Poska Satu Räsänen Welmoed Soepboer Henrik von Stedingk Henna Suutari Shinya Sugita 《Vegetation History and Archaeobotany》2008,17(5):461-478
Information on the spatial distribution of past vegetation on local, regional and global scales is increasingly used within
climate modelling, nature conservancy and archaeology. It is possible to obtain such information from fossil pollen records
in lakes and bogs using the landscape reconstruction algorithm (LRA) and its two models, REVEALS and LOVE. These models assume
that reliable pollen productivity estimates (PPEs) are available for the plant taxa involved in the quantitative reconstructions
of past vegetation, and that PPEs are constant through time. This paper presents and discusses the PPEs for 15 tree and 18
herb taxa obtained in nine study areas of Europe. Observed differences in PPEs between regions may be explained by methodological
issues and environmental variables, of which climate and related factors such as reproduction strategies and growth forms
appear to be the most important. An evaluation of the PPEs at hand so far suggests that they can be used in modelling applications
and quantitative reconstructions of past vegetation, provided that consideration of past environmental variability within
the region is used to inform selection of PPEs, and bearing in mind that PPEs might have changed through time as a response
to climate change. Application of a range of possible PPEs will allow a better evaluation of the results. 相似文献
44.
Florence Mazier Anna Broström Marie-José Gaillard Shinya Sugita Pascal Vittoz Alexandre Buttler 《Vegetation History and Archaeobotany》2008,17(5):479-495
Relevant source area of pollen (RSAP) and pollen productivity for 11 key taxa characteristic of the pasture woodland landscape
of the Jura Mountains, Switzerland, were estimated using pollen assemblages from moss polsters at 20 sites. To obtain robust
pollen productivity estimates (PPEs), we used vegetation survey data at a fine spatial-resolution (1 × 1 m2) and randomized locations for sampling sites, techniques rarely used in palynology. Three Extended R value (ERV) submodels and three distance-weighting methods for plant abundance calculation were applied. Different combinations
of the submodels and distance-weighting methods provide slightly different estimates of RSAP and PPEs. Although ERV submodel
1 using 1/d (d = distance in meters) best fits the dataset, PPE values for heavy pollen types (e.g. Abies) were sensitive to the method used for distance-weighting. Taxon-specific distance-weighting methods, such as Prentice’s
model, emphasize the intertaxonomic differences in pollen dispersal and deposition, and are thus theoretically sound. For
the dataset obtained in this project, Prentice’s model was more appropriate than other distance-weighting methods to estimate
PPEs. Most of the taxa have PPEs equal to (Fagus, Plantago media and Potentilla-type), or higher (Abies, Picea, Rubiaceae and Trollius
europaeus) than Poaceae (PPE = 1). Acer, Cyperaceae, and Plantago
montana-type are low pollen producers. This set of PPEs will be useful for reconstructing heterogeneous, mountainous pasture woodland
landscapes from fossil pollen records. The RSAP for moss polsters in this semi-open landscape region is ca. 300 m. 相似文献
45.
Marie-José Gaillard Shinya Sugita M. Jane Bunting Richard Middleton Anna Broström Christopher Caseldine Thomas Giesecke Sophie E. V. Hellman Sheila Hicks Kari Hjelle Catherine Langdon Anne-Birgitte Nielsen Anneli Poska Henrik von Stedingk Sim Veski 《Vegetation History and Archaeobotany》2008,17(5):419-443
Information on past land cover in terms of absolute areas of different landscape units (forest, open land, pasture land, cultivated
land, etc.) at local to regional scales is needed to test hypotheses and answer questions related to climate change (e.g.
feedbacks effects of land-cover change), archaeological research, and nature conservancy (e.g. management strategy). The palaeoecological
technique best suited to achieve quantitative reconstruction of past vegetation is pollen analysis. A simulation approach
developed by Sugita (the computer model POLLSCAPE) which uses models based on the theory of pollen analysis is presented together
with examples of application. POLLSCAPE has been adopted as the central tool for POLLANDCAL (POLlen/LANdscape CALibration),
an international research network focusing on this topic. The theory behind models of the pollen–vegetation relationship and
POLLSCAPE is reviewed. The two model outputs which receive greatest attention in this paper are the relevant source area of
pollen (RSAP) and pollen loading in mires and lakes. Six examples of application of POLLSCAPE are presented, each of which
explores a possible use of the POLLANDCAL tools and a means of validating or evaluating the models with empirical data. The
landscape and vegetation factors influencing the size of the RSAP, the importance of pollen productivity estimates (PPEs)
for the model outputs, the detection of small and rare patches of plant taxa in pollen records, and quantitative reconstructions
of past vegetation and landscapes are discussed on the basis of these examples. The simulation approach is seen to be useful
both for exploring different vegetation/landscape scenarios and for refuting hypotheses. 相似文献
46.
47.
Bélisle JM Costantino S Leimanis ML Bellemare MJ Bohle DS Georges E Wiseman PW 《Biophysical journal》2008,94(4):L26-L28
Malaria remains a major health concern worldwide, with 350-500 million cases reported annually in endemic countries. In this study, we report a novel and highly sensitive optical-based detection of malaria-infected blood cells by third harmonic generation (THG) imaging of hemozoin pigment that is naturally deposited by the parasite during its lifecycle. The THG signal from the hemozoin was greater than we have observed in any cell type with signal/noise ratios that reach 1000:1. This method allows a rapid and robust detection of early stage infections of blood cells. The immense nonlinear response of the intrinsic parasitic by-product pigments suggests that automated optical detection by THG could be used for sensitive and rapid screening of parasite infection in blood samples. 相似文献
48.
Jean-Pierre Raynauld Johanne Martel-Pelletier Marie-Josée Berthiaume Gilles Beaudoin Denis Choquette Boulos Haraoui Hyman Tannenbaum Joan M Meyer John F Beary Gary A Cline Jean-Pierre Pelletier 《Arthritis research & therapy》2005,8(1):1-12
The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression. 相似文献
49.
Fanny Jaulin-Bastard Jean-Pierre Arsanto André Le Bivic Christel Navarro Frederic Vély Hiroko Saito Sylvie Marchetto Mechthild Hatzfeld Marie-Josée Santoni Daniel Birnbaum Jean-Paul Borg 《The Journal of biological chemistry》2002,277(4):2869-2875
Integrity of epithelial tissues relies on the proper apical-basolateral polarity of epithelial cells. Members of the LAP (LRR and PDZ) protein family such as LET-413 and Scribble are involved in maintaining epithelial cell polarity in Caenorhabditis elegans and Drosophila melanogaster, respectively. We previously described Erbin as a mammalian LET-413 homologue interacting with ERBB2/HER2, an epidermal growth factor receptor family member. Erbin and ERBB2/HER2 are located in the basolateral membranes of epithelial cells. We show here that Erbin interacts with p0071 (also called plakophilin-4), an armadillo repeat protein linked to the cytoskeleton. Erbin binds to p0071 in vitro and in vivo in a PDZ domain-dependent manner, and both proteins colocalized in desmosomes of epithelial cells. Using a dominant negative approach, we found that integrity of epithelial cell monolayer is impaired when interaction between Erbin and p0071 is disrupted. We propose that Erbin is connected by p0071 to cytoskeletal networks in an interaction crucial for epithelial homeostasis. 相似文献
50.