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1.
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2.
ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway   总被引:70,自引:0,他引:70  
Lim DS  Kim ST  Xu B  Maser RS  Lin J  Petrini JH  Kastan MB 《Nature》2000,404(6778):613-617
The rare diseases ataxia-telangiectasia (AT), caused by mutations in the ATM gene, and Nijmegen breakage syndrome (NBS), with mutations in the p95/nbs1 gene, share a variety of phenotypic abnormalities such as chromosomal instability, radiation sensitivity and defects in cell-cycle checkpoints in response to ionizing radiation. The ATM gene encodes a protein kinase that is activated by ionizing radiation or radiomimetic drugs, whereas p95/nbs1 is part of a protein complex that is involved in responses to DNA double-strand breaks. Here, because of the similarities between AT and NBS, we evaluated the functional interactions between ATM and p95/nbs1. Activation of the ATM kinase by ionizing radiation and induction of ATM-dependent responses in NBS cells indicated that p95/nbs1 may not be required for signalling to ATM after ionizing radiation. However, p95/nbs1 was phosphorylated on serine 343 in an ATM-dependent manner in vitro and in vivo after ionizing radiation. A p95/nbs1 construct mutated at the ATM phosphorylation site abrogated an S-phase checkpoint induced by ionizing radiation in normal cells and failed to compensate for this functional deficiency in NBS cells. These observations link ATM and p95/nbs1 in a common signalling pathway and provide an explanation for phenotypic similarities in these two diseases.  相似文献   
3.
We examined the mycophagy (ingestion of fungi) of squirrels of five genera and eight species in the coniferous forests of Oregon. Data from 644 dietary samples demonstrated that squirrels of all eight species are mycophagous and eat the belowground fruiting bodies of at least 26 genera of mycorrhizal fungi. Four species are primarily arboreal and active throughout the year; the other four are primarily terrestrial and hibernate during winter. Of the squirrels examined, only the northern flying squirrel ( Glaucomys sabrinus [Shaw]) is nocturnal and almost exclusively a fungivore. The flying squirrel is used to illustrate the dynamics of all the squirrels in association with hypogeous mycorrhizal fungi, nitrogen-fixing bacteria, yeast, and coniferous trees in Oregon forests because we have studied it the most. Squirrels may prove to be vital links among different processes within temperate coniferous forests.  相似文献   
4.
Stomach contents of 650 clouded salamanders ( Aneides ferreus ), collected monthly throughout the year from Curry County, Oregon, were examined. Samples from three age classes were involved: (1) 489 adults, (2) 131 juveniles, and (3) 30 hatchlings. Foods did not vary by sex, but did vary by age and by season. Hatchlings ate small items, particularly mites, springtails, flies, and small beetles. Juveniles fed mainly on flies, isopods (sowbugs), beetles, mites, and centipedes in winter; beetles, ants, and isopods in spring; ants and beetles in summer; and isopods, beetles, and ants in fall. Adults ate isopods and beetles as their major foods in winter, spring, and fall and isopods, ants, beetles, and earwigs in summer. Four species were exceedingly important as foods for these salamanders: an unidentified isopod, the snout beetle ( Trachyphloeus bifoveatus ), the European earwig ( Forficula auricularia ), and an ant ( Lasius alienus ).    相似文献   
5.
Animal and nonanimal items were identified in the digestive tracts of 61 cougars ( Felis concolor ) collected between 1978 and 1984 from the western slopes of the Cascade Range in Oregon. Forty - two (69%) of the cougars were taken by hunters in December and January, 18 (30%) were killed at other times of the year because of their proximity to livestock, and one animal was illegally killed in November. Black-tailed deer ( Odocoileus hemionus columbianus ) was the most common prey item, although domestic sheep ( Ovis airies ), porcupines ( Erethizon dorsatum ), and a variety of small mammals were also recorded. Masticated grass was the most common nonanimal item.   相似文献   
6.
We examined stomach contents of 426 Clethrionomys , 217 C. californicus from western Oregon and 209 C. gapperi from widely scattered areas across North America. Clethrionomys californicus consumed fungi of 28 genera. Clethrionomys gapperi from the Rocky Mountains westward consumed fungi of 23 genera, whereas C. gapperi east of the Rocky Mountains consumed fungi of 7 genera. This study supports the conclusions of an earlier study, limited to Oregon and Washington, that food habits of C. californicus and C. gapperi are more closely related to habitat than to species or subspecies of vole.  相似文献   
7.
To determine the role of the California red-backed vole ( Clethrionomys califonicus ), the northern flying squirrel ( Glaucomys sabrinus ), and the deer mouse ( Peromyscus maniculatus ) in the nitrogen cycle of forest stands in western Oregon, bacterial colonies were isolated and purified from feces, and their nitrogen-fixing ability measured by acetylene-reduction assay. The ability of the bacterial species Azospirillum   sp. to withstand freezing was also tested. Fecal extracts were used to test whether fecal pellets can provide the nutrients necessary for growth of the bacteria. All the feces tested contained viable nitrogen-fixing bacteria, and both species can survive drying and one can survive freezing. Azospirillum colonies grew well on liquid medium but required yeast extract for growth and nitrogenase activity. Fecal extracts from flying squirrels and chickarees ( Tamiasciurus douglasi ) were as effective as the yeast. The results suggest another link in the chain of mutualism that unites small mammals, mycorrhizal fungi, and forest trees.  相似文献   
8.
9.
The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer and T-cell acute lymphoblastic leukaemia (T-ALL). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL, validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun, Myc, cyclin E and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth, overexpression of Jun, Myc or notch 1 can also induce programmed cell death. Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCF(FBW7) (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL.  相似文献   
10.
Fungal spores from the same taxa of fungi that occur in the Pacific Northwest are reported from digestive tracts of31 rodents of 5 genera from the Nothofagus forest of southern Argentina. Mycophagy (fungal feeding) by forest rodents has been well documented in North America (Fogel and Trappe 1978, Maser et al. 1978, Mclntire 1984, and others), Europe (Blaschke and B?umler 1986, Durrieu et al. 1984), and Australia (Malajczuk et al. 1987). The purpose of this note is to report fungi consumed by rodents of the Argentine Andinian Patagonic forest (see Dimitri 1972,McQueen 1977, and Ward 1965 for a discussion of this forest), where mycorrhizal fungi may be an important part of the forest-rodent ecology (Cabrera and Yepes 1960, Pearson 1983, 1948, Pearson and Pearson 1982).  相似文献   
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