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The dynamic and stringent coordination of kinase and phosphatase activity controls a myriad of physiologic processes. Aberrations that disrupt the balance of this interplay represent the basis of numerous diseases. For a variety of reasons, early work in this area portrayed kinases as the dominant actors in these signaling events with phosphatases playing a secondary role. In oncology, these efforts led to breakthroughs that have dramatically altered the course of certain diseases and directed vast resources toward the development of additional kinase-targeted therapies. Yet, more recent scientific efforts have demonstrated a prominent and sometimes driving role for phosphatases across numerous malignancies. This maturation of the phosphatase field has brought with it the promise of further therapeutic advances in the field of oncology. In this review, we discuss the role of phosphatases in the regulation of cellular proliferation and survival signaling using the examples of the MAPK and PI3K/AKT pathways, c-Myc and the apoptosis machinery. Emphasis is placed on instances where these signaling networks are perturbed by dysregulation of specific phosphatases to favor growth and persistence of human cancer.  相似文献   
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Page SE  Siegert F  Rieley JO  Boehm HD  Jaya A  Limin S 《Nature》2002,420(6911):61-65
Tropical peatlands are one of the largest near-surface reserves of terrestrial organic carbon, and hence their stability has important implications for climate change. In their natural state, lowland tropical peatlands support a luxuriant growth of peat swamp forest overlying peat deposits up to 20 metres thick. Persistent environmental change-in particular, drainage and forest clearing-threatens their stability, and makes them susceptible to fire. This was demonstrated by the occurrence of widespread fires throughout the forested peatlands of Indonesia during the 1997 El Ni?o event. Here, using satellite images of a 2.5 million hectare study area in Central Kalimantan, Borneo, from before and after the 1997 fires, we calculate that 32% (0.79 Mha) of the area had burned, of which peatland accounted for 91.5% (0.73 Mha). Using ground measurements of the burn depth of peat, we estimate that 0.19-0.23 gigatonnes (Gt) of carbon were released to the atmosphere through peat combustion, with a further 0.05 Gt released from burning of the overlying vegetation. Extrapolating these estimates to Indonesia as a whole, we estimate that between 0.81 and 2.57 Gt of carbon were released to the atmosphere in 1997 as a result of burning peat and vegetation in Indonesia. This is equivalent to 13-40% of the mean annual global carbon emissions from fossil fuels, and contributed greatly to the largest annual increase in atmospheric CO(2) concentration detected since records began in 1957 (ref. 1).  相似文献   
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We determined home-range overlap among northern flying squirrels ( Glaucomys sabrinus ) to assess their spatial organization. We found extensive home-range overlap among females, and though this overlap could reflect social behavior, we found no evidence of attraction among females, with only one instance of den-sharing. Instead, our results suggest that females share foraging areas but may be territorial in portions of the home range, especially around den trees and during young-rearing. Home-range overlap could also result from the extrinsic effect of forest fragmentation due to timber harvest, which might impede dispersal and force squirrels to cluster on remaining fragments of suitable habitat. Determinamos el sobrelapamiento del rango hogareño entre las ardillas voladoras del norte ( Glaucomys sabrinus ) para evaluar su organización espacial. Encontramos un extenso sobrelapamientos en los rangos hogareños entre las hembras; aunque esto podría reflejar su comportamiento social, no encontramos evidencia de atracción entre hembras, y en sólo un caso compartieron su guarida. Vienen su lugar, nuestros resultados sugieren que las hembras comparten áreas de forrajeo pero pueden ser territoriales en ciertas partes de su rango hogareño, particularmente cerca de los árboles donde tienen guaridas y cuando tienen cría. El sobrelapamiento del rango hogareño también podría ser el resultado del efecto extrínseco de la fragmentación forestal debido a la tala de madera, el cual podría impedir la dispersión y forzar a las ardillas a agruparse en fragmentos de hábitat adecuado que queden.  相似文献   
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Summary Structures of iselin and iliensin have been revised. The structure (Ib) is secured for iselin by a direct comparison (m.p., UV, IR, PMR) with archangelin. The synthesis of iliensin (IIb) has been effected through the condensation of xanthotoxol (II, R=OH) and -cyclolavandulyl bromide (III). The synthetic product has been shown to be identical with natural iliensin.We thank Dr S.Z. Qasim and Dr M.S. Chadha for the spectral data and C.S.I.R. for a research fellowship to J.V.  相似文献   
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