首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   390篇
  免费   0篇
系统科学   1篇
教育与普及   1篇
理论与方法论   2篇
现状及发展   60篇
研究方法   33篇
综合类   255篇
自然研究   38篇
  2019年   1篇
  2018年   1篇
  2017年   1篇
  2015年   1篇
  2014年   1篇
  2013年   3篇
  2012年   8篇
  2011年   57篇
  2010年   2篇
  2009年   1篇
  2008年   7篇
  2007年   10篇
  2006年   9篇
  2005年   12篇
  2004年   12篇
  2003年   14篇
  2002年   16篇
  2001年   15篇
  2000年   14篇
  1999年   11篇
  1995年   1篇
  1992年   15篇
  1991年   8篇
  1990年   15篇
  1989年   5篇
  1988年   7篇
  1987年   12篇
  1986年   5篇
  1985年   13篇
  1984年   4篇
  1983年   3篇
  1981年   4篇
  1979年   9篇
  1978年   4篇
  1977年   4篇
  1976年   6篇
  1975年   6篇
  1974年   4篇
  1973年   2篇
  1972年   3篇
  1971年   9篇
  1970年   15篇
  1969年   8篇
  1968年   7篇
  1967年   8篇
  1966年   5篇
  1965年   11篇
  1963年   1篇
排序方式: 共有390条查询结果,搜索用时 31 毫秒
11.
Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.  相似文献   
12.
The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ~2?°C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6?°C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase.  相似文献   
13.
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.  相似文献   
14.
We describe a case study evaluating the ecological impact of Bromus tectorum L. (cheatgrass) invasion following fire disturbance and the effectiveness of revegetation as a means of rehabilitation in a degraded semiarid shrubsteppe system. The effectiveness of rehabilitation efforts was assessed relative to arthropod richness, vegetation and arthropod community composition, and ground-cover characteristics in 3 habitats: undisturbed, burned and weed infested ( B. tectorum ), and burned then rehabilitated with native and nonnative vegetation. Arthropods were collected in each habitat using pitfall traps. Differences in arthropod richness were compared using rarefaction curves. Nonmetric multidimensional scaling and nonparametric multivariate statistical procedures, including analysis of similarity and similarity percentage routines, were used to compare arthropod and vegetation community composition and ground-cover characteristics between habitats. Arthropod communities in the rehabilitated habitat were distinct from those observed in the undisturbed and weed-infested habitats. Rehabilitation in this study resulted in a shift toward conditions observed in an undisturbed habitat and perhaps is an intermediate step to complete restoration. Arthropod richness, arthropod and vegetation community composition, and ground-cover characteristics were all useful indicators but returned slightly different results. Assessing multiple variables yielded the most complete understanding of the habitats studied.  相似文献   
15.
Although previous research has considered habitat associations and breeding biology of Mountain Plovers in Wyoming at discrete sites, no study has considered these attributes at a statewide scale. We located 55 Mountain Plover nests in 6 counties across Wyoming during 2002 and 2003. Nests occurred in 2 general habitat types: grassland and desert-shrub. Mean estimated hatch date was 26 June ( n = 31) in 2002 and 21 June ( n = 24) in 2003. Mean hatch date was not related to latitude or elevation. Hatch success of nests was inferred in 2003 by the presence of eggshell fragments in the nest scrape. Eggs in 14 of 22 (64%) known-fate nests hatched. All grassland sites and 90% of desert sites were host to ungulate grazers, although prairie dogs were absent at 64% of nest sites. Nest plots had less grass coverage and reduced grass height compared with random plots. More than 50% of nests occurred on elevated plateaus. The Mountain Plover's tendency to nest on arid, elevated plateaus further substantiates claims that the bird is also a disturbed- prairie species.  相似文献   
16.
Populations of Greater Sage-Grouse ( Centrocercus urophasianus ) have been declining throughout their range since the 1960s. Productivity, which includes production and survival of young, is often cited as a factor in these declines. We monitored radio-equipped Greater Sage-Grouse at 3 sites in western Wyoming to assess early brood-rearing habitat use (through 14 days post-hatch) and productivity. Logistic and linear regression analyses with Akaike's Information Criterion were used to evaluate early brooding habitat use and to examine relationships between productivity and vegetation, insect size and abundance, and weather parameters. Females with broods were found in areas with greater sagebrush canopy and grass cover, and fewer invertebrates compared to random areas. The number of juveniles per female (estimated from wing barrel collections during fall harvest) was positively related to the abundance of medium-length Hymenoptera and grass cover, and the proportion of females with confirmed chicks 14 days post-hatch was positively related to abundance of medium-length Coleoptera and total herbaceous cover. Although the specific parameters varied slightly, Greater Sage-Grouse productivity in Wyoming appeared to be associated with a combination of insect and herbaceous cover elements. Managing for abundant and diverse insect communities within dense protective sagebrush stands should help ensure high-quality early brood-rearing habitat and increased Greater Sage-Grouse productivity.  相似文献   
17.
The new, presumably extinct species, Chrysothamnus pulchelloides, is formally described and illustrated. The plant materials came from Holocene packrat middens. Anatomical and phyletic relationships of the fossil species to extant taxa are discussed.  相似文献   
18.
Our objective was to clarify the effects of 10 identified variables on snipe activity (winnowing and calling) by demonstrating correlations between the variables and snipe activity. We monitored snipe at 2 study areas in southwestern Montana and northwestern Wyoming at all hours of the day and night during the 1996 and 1997 breeding seasons. We measured 10 variables at established points along transects that were situated through the middle of each study site (8 study sites total). A total of 1200 monitoring periods were conducted throughout the course of this study. Effects of each factor on snipe activity were considered by examining general trends in each factor's graphical representation. Our results identified 6 factors (season, time of day, lunar cycle, solar radiation, wind speed, and temperature) that are associated with snipe activity. Snipe were most active early in the breeding season during 2 twilight periods during the first and last quarters of the lunar cycle. Low solar radiation levels, wind speeds, and temperatures were also most ideal conditions for snipe activity. All 6 factors should be considered when attempting to detect, survey, or estimate snipe populations.  相似文献   
19.
Cilia-associated human genetic disorders are striking in the diversity of their abnormalities and their complex inheritance. Inactivation of the retrograde ciliary motor by mutations in DYNC2H1 causes skeletal dysplasias that have strongly variable expressivity. Here we define previously unknown genetic relationships between Dync2h1 and other genes required for ciliary trafficking. Mutations in mouse Dync2h1 disrupt cilia structure, block Sonic hedgehog signaling and cause midgestation lethality. Heterozygosity for Ift172, a gene required for anterograde ciliary trafficking, suppresses cilia phenotypes, Sonic hedgehog signaling defects and early lethality of Dync2h1 homozygotes. Ift122, like Dync2h1, is required for retrograde ciliary trafficking, but reduction of Ift122 gene dosage also suppresses the Dync2h1 phenotype. These genetic interactions illustrate the cell biology underlying ciliopathies and argue that mutations in intraflagellar transport genes cause their phenotypes because of their roles in cilia architecture rather than direct roles in signaling.  相似文献   
20.
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号