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排序方式: 共有9199条查询结果,搜索用时 15 毫秒
1.
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.  相似文献   
2.
Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (COG) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of COG on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, COG did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by COG or CORM-A1, was dependent on sGC. We conclude that the source (COG vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.  相似文献   
3.
利用活性炭的强吸附能力和锡的催化性能,在活性炭上负载氯化亚锡,制备了负载型氯乙烯合成触媒。研究了不同温度、反应时间和乙烘流量下,触媒的使用寿命和乙烘的转化率。分析了氯化亚锡作为活性组分的优缺点。  相似文献   
4.
以自制苯并噻唑离子液体([HBth]HSO4)为活性组分,HZSM-5分子筛为载体,通过过量溶剂浸渍法制备了固载型苯并噻唑离子液体催化剂([HBth]HSO4/HZSM-5)并用于催化合成烷基糖苷,通过傅立叶变换红外光谱、N2物理脱附、场发射电子显微镜和X射线衍射对催化剂结构进行表征,结果表明,[HBth]HSO4被成功地引入到HZSM-5载体的表面及孔道内。当催化剂用量为1.5 wt%,反应温度为105℃,醇糖摩尔比n(葡萄糖):n(辛醇)=6:1时,辛基糖苷得率达148.8%(产物质量/葡萄糖的质量?100%)。底物拓展及催化剂稳定性研究结果表明,[HBth]HSO4/HZSM-5对烷基糖苷及其衍生物都具有良好的催化效果,且催化剂能稳定循环使用四次,活性组分流失是催化剂失活的主要原因。通过对烷基糖苷催化合成机理和动力学的研究,确定了动力学方程。  相似文献   
5.
Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.  相似文献   
6.
Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.  相似文献   
7.
Lithium zirconium phosphate (LiZr2P3O12) thin films have been prepared on platinized silicon substrates via a chemical solution deposition approach with processing temperatures between 700°C and 775°C. Films that were subject to a single high-temperature anneal were found to crystallize at temperatures above 725°C. Crystallization was observed in films annealed after each deposited layer at 700°C and above. In both cases, grain size was found to increase with annealing temperature. Ion conductivity was found to increase with annealing temperature in singly annealed films. In per-layer annealed films ion conductivity was found to initially increase then decrease with increasing annealing temperature. A maximum ion conductivity of 1.6 × 10−6 S/cm was observed for the singly annealed 775°C condition, while a maximum ion conductivity of 5.8 × 10−7 S/cm was observed for the 725°C per-layer annealed condition. These results are consistent with an increasing influence of cross-plane, internal interface resistance and vapor phase carrier loss in the per-layer annealed samples. This work demonstrates that post-deposition processing methods can strongly affect the ion conducting properties of LiZr2P3O12 thin films.  相似文献   
8.
Sensitivity and multi-directional motivation are major two factors for developing optimized humidity-response materials, which are promising for sensing, energy production, etc. Organic functional groups are commonly used as the water sensitive units through hydrogen bond interactions with water molecules in actuators. The multi-coordination ability of inorganic ions implies that the inorganic ionic compounds are potentially superior water sensitive units. However, the particle forms of inorganic ionic compounds produced by classical nucleation limit the number of exposed ions to interact with water. Recent progress on the inorganic ionic oligomers has broken through the limitation of classical nucleation, and realized the molecular-scaled incorporation of inorganic ionic compounds into an organic matrix. Here, the incorporation of hydrophilic calcium carbonate ionic oligomers into hydrophobic poly(vinylidene fluoride) (PVDF) is demonstrated. The ultra-small calcium carbonate oligomers within a PVDF film endow it with an ultra-sensitive, reversible, and bidirectional response. The motivation ability is superior to other bidirectional humidity-actuators at present, which realizes self-motivation on an ice surface, converting the chemical potential energy of the humidity gradient from ice to kinetic energy.  相似文献   
9.
该文筛选能够应用在桑叶多糖提取中可形成双水相现象较好的离子液体和无机盐体系,并研究含离子液体萃取体系中桑叶多糖的最佳提取工艺。研究1-丁基-3-甲基咪唑四氟硼酸盐、1-辛基-3-甲基咪唑六氟磷酸盐、谷氨酸双三氟甲磺酰亚胺盐等15种离子液体分别加入磷酸二氢钾、无水碳酸钠、硫代硫酸钠等13种无机盐中形成双水相现象的难易程度,筛选出形成双水相现象较好的离子液体。采用溶剂浸提法对桑叶进行提取,采用单因素试验研究离子液体浓度、提取温度、提取时间和料液比对桑叶中多糖化合物提取的影响,并根据响应面设计试验和验证试验获得桑叶多糖的最优提取工艺条件为离子液体浓度0.000 3 mol/L、提取温度76℃、料液比1∶20(g/mL)、提取时间109 min。  相似文献   
10.
合成了1-烷基-3-乙羟基咪唑溴离子液体([REhIM]Br,其中R=C10H21、C12H25和C14H29),采用密度泛函理论方法(DFT),在B3LYP/6-31水平上优化[REhIM]Br离子液体的分子结构,得到其最稳定的构型,通过理论计算得到了分子中的部分键长键角,对其电荷分布进行了分析;通过计算阴阳离子和[REhIM]Br的单点能,计算得到其离子间作用能;最后,得到了电子结构中的LUMO能、HOMO能以及能隙的数据。结果表明,在阴离子保持不变时,随着[REhIM]Br离子液体的烷基链的增长,键长键角以及电荷分布等微观结构与烷基链的长度变化无关;而离子间作用能、LUMO能、HOMO能和能隙ΔELUMO-HOMO等能量相关数据与烷基链上C原子个数有密切联系,随着烷基链的增长,离子间作用能及能隙均变小,结构变得不稳定。  相似文献   
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