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The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells.  相似文献   
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Ohne ZusammenfassungHerrn Professor Dr. R. Gistl zu seinem 70. Geburtstag in Verehrung und Dankbarkeit gewidmet.  相似文献   
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With the goal to identify novel trypanothione reductase (TR) inhibitors, we performed a combination of in vitro and in silico screening approaches. Starting from a highly diverse compound set of 2,816 compounds, 21 novel TR inhibiting compounds could be identified in the initial in vitro screening campaign against T. cruzi TR. All 21 in vitro hits were used in a subsequent similarity search-based in silico screening on a database containing 200,000 physically available compounds. The similarity search resulted in a data set containing 1,204 potential TR inhibitors, which was subjected to a second in vitro screening campaign leading to 61 additional active compounds. This corresponds to an approximately 10-fold enrichment compared to the initial pure in vitro screening. In total, 82 novel TR inhibitors with activities down to the nM range could be identified proving the validity of our combined in vitro/in silico approach. Moreover, the four most active compounds, showing IC50 values of <1 μM, were selected for determining the inhibitor constant. In first on parasites assays, three compounds inhibited the proliferation of bloodstream T. brucei cell line 449 with EC50 values down to 2 μM.  相似文献   
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Marie Spohn  Luise Giani 《Plant and Soil》2011,338(1-2):183-192
Soil organic carbon stocks decrease after conversion of soils from pasture to cropland. It has been assumed that this applies especially to mineral hydromorphic soils. In this paper we evaluate hot-water extractable carbon (Chwe) as a measure for detecting long-term changes in the SOM following land use change. Furthermore, we assess whether a treatment of the soils with NaOCl leads to the isolation of long-term stable C fractions. For these purposes, we established a chronosequence of sandy hydromorphic soils that have been converted from pasture to cropland at different periods of history. To gain further insight into the impacts of different types of land use on carbon sequestration, soils under forest, either afforested or permanent, were studied. Bulk density, total organic carbon (TOC), Chwe, and NaOCl-resistant C were quantified in the surface soils of 72 Gleyic Podzols and Haplic Gleysols. The bulk density increased from 0.9 (±0.2) g cm?3 to 1.4 (±0.1) g cm?3 during the first 25 years after the conversion of the soils from permanent pasture to cropland. In the permanent pasture sites, the TOC concentration amounted to 35.4 (±12.1) g kg?1. It decreased to 12.88 (±5.9) g kg?1 during the first 46 years of cultivation (R2?=?0.71). In the permanent forest soils the TOC concentrations were significantly higher than in the soils that have been afforested. Chwe concentrations of the chronosequence sites were linearly correlated to the TOC concentrations (R2?=?0.84), while permanent forest sites exhibited significantly higher Chwe/TOC ratios. This shows that the determination of the Chwe is a very promising measure for detecting changes in SOM dynamics following afforestation. In the permanent pasture sites, 14.3 (±5.38) g kg?1 NaOCl-resistant C was measured, while 46 years after conversion, only 2.8 (±1.2) g kg?1remained. No enrichment of NaOCl-resistant C was observed in the chronosequence, as NaOCl-resistant C decreased faster in the course of cultivation than the TOC. Therefore, we conclude that that the C fraction that resists the oxidation with NaOCl is not long-term stable in soils, and most probably, there is no such long-term stable C fraction in the soils under study.  相似文献   
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As climate warms, conifers are expected to expand their ranges into alpine tundra where ecological factors such as seedbed availability, and post‐dispersal seed and seedling predation may control local recruitment. Seedbed composition may influence microhabitat, nutrients, physical structure, and predation level and, therefore, affect the success of conifer recruitment, thereby providing the template for future expansion. In the boreal forest, seedbed–seedling competition dominates such that seedbed removal increases black spruce recruitment. In the harsher climate of the Mealy Mountains boreal forest–tundra ecotone (Labrador, Canada) the Stress gradient hypothesis (SGH) predicts that facilitation may dominate seedbed–seedling interactions. This study investigated potential mechanisms of seedbed facilitation (temperature, water, nutrients, physical protection) in three conifer seedbeds (Pleurozium schreberi, Cladonia spp., bare soil) and examined whether seed predation and/or seedling herbivory varied among seedbeds over three years. Seed emergence was low overall (< 10% on all treatments), but highest on Pleurozium (6.3%), followed by bare ground (4.6%) and Cladonia (0.3%). Facilitation was observed between Pleurozium and black spruce as seedling height increase (31%) and survival (55%) were highest; herbivory, seed predation and overwinter mortality were lowest compared to both Cladonia and bare ground seedbeds. Unlike in the closed canopy boreal forest, seedlings recruited poorly on bare soil as seedling height increase and survival were 20.5% and 26%. Temperature and water availability were similar across seedbeds, while nutrient availability was higher on Pleurozium. The physical structure of Pleurozium likely protects first to third‐year seedlings from temperature extremes and predators. As climate warms and seed availability increases, Pleurozium may facilitate black spruce recruitment and treeline expansion.  相似文献   
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The Atacama Desert is the driest non‐polar desert on Earth, presenting precarious conditions for biological activity. In the arid coastal belt, life is restricted to areas with fog events that cause almost daily wet–dry cycles. In such an area, we discovered a hitherto unknown and unique ground covering biocenosis dominated by lichens, fungi, and algae attached to grit‐sized (~6 mm) quartz and granitoid stones. Comparable biocenosis forming a kind of a layer on top of soil and rock surfaces in general is summarized as cryptogamic ground covers (CGC) in literature. In contrast to known CGC from arid environments to which frequent cyclic wetting events are lethal, in the Atacama Desert every fog event is answered by photosynthetic activity of the soil community and thus considered as the desert's breath. Photosynthesis of the new CGC type is activated by the lowest amount of water known for such a community worldwide thus enabling the unique biocenosis to fulfill a variety of ecosystem services. In a considerable portion of the coastal Atacama Desert, it protects the soil from sporadically occurring splash erosion and contributes to the accumulation of soil carbon and nitrogen as well as soil formation through bio‐weathering. The structure and function of the new CGC type are discussed, and we suggest the name grit–crust. We conclude that this type of CGC can be expected in all non‐polar fog deserts of the world and may resemble the cryptogam communities that shaped ancient Earth. It may thus represent a relevant player in current and ancient biogeochemical cycling.  相似文献   
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