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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.
刘颖 《铸造工程》2021,(3):58-60
针对熔模精铸存在生产工艺流程长、涉及到的主辅材料多、生产环境较差等现实问题,通过推行5S管理方法,持续促进现场改善,有效提高了生产效率和保障了产品质量。  相似文献   
3.
随着人们日益增长的生活水平,我国电力管理体制改革也在逐步的深化,人们对于电力资源的需求不断提升,电力基建工程建设与供电的质量有待进一步加强。电力施工企业应充分认识到电力工程项目施工过程中安全管理的重要性,明确电力工程项目施工安全给企业带来的安全效益。本文对电力工程基建施工现场所存在的一些实际问题进行分析和研究,并总结施工现场“7s管理”模式的应用前景以及管理方面的要求,希望能够为我国的电力工程基础建设有所帮助。  相似文献   
4.
Using headspace solid-phase microextraction (HS–SPME), equilibrium distributions could be determined for hydrophobic solutes in closed systems containing vapor and aqueous solution, either in the absence or presence of two short-chain phospholipids, dihexanoyl-phosphatidylcholine (diC6PC) and diheptanoyl-phosphatidylcholine (diC7PC). Without phospholipid, HS–SPME with short extraction times was used to measure water–vapor partition coefficients for d-limonene at five temperatures within 15–40°C, with results in good agreement with existing literature. The temperature dependence of yielded the enthalpy of volatilization 34.5 kJ/mol for limonene. At 25°C, solubility values for d-limonene, 1-octanol, and n-decane were obtained using similar measurements above aqueous solutions of various solute concentrations. Short-time HS–SPME extraction of limonene in closed vials containing diC6PC or diC7PC micelles was also used to evaluate distributions of solute between vapor, aqueous dissolution, and micelles, for various surfactant concentrations at 15–40°C. Resulting vapor phase concentrations were analyzed using a mass balance and measured values, to obtain micelle–water partition coefficients and critical micelle concentrations. in diC6PC solutions (1–2 mM−1) weakly increased with temperature, but decreased significantly with increased temperature for diC7PC micelles (2–4 mM−1). Solubilization in short-chain PC micelles has previously received little attention, and our results show that the extent of partitioning into these diacyl (i.e., two-tailed) lipids is comparable to that for single-tailed anionic or nonionic surfactants.  相似文献   
5.
《Ceramics International》2021,47(19):27351-27360
A series of xPbO–(45-x)CuO–55B2O3 glasses (5 ≤ x ≥ 40 mol %) were prepared by the melt-quenching technique. The X-ray diffraction (XRD) patterns of the prepared glasses are found to have amorphous structure. An extensive ultrasonic study has been made to explore the structural role of PbO and CuO in the borate network. Various elastic properties were calculated from the measured data of density and ultrasonic velocity. Ultrasonic velocity and elastic moduli revealed broad humps at about 20 mol % PbO, which are attributed to the borate anomaly. Below 20 mol % PbO, all Pb2+ ions are considered to be entering the borate network as a glass modifier. This results in the transforms the borate network from an open structure to a denser three-dimensional structure due to BO3 → BO4 conversion. Beyond 20 mol, addition of PbO results in the formation of metaborate, pyroborate, and orthoborate units with NBOs. This weakness the glass structure and decrease both ultrasonic velocity and elastic moduli. The elastic properties were predicted and quantitatively analyzed by taking into account the effect of boron coordination number on the compositional and structural parameters involved in Makishima–Mackenzie's theory, ring deformation model and bond compression model. An excellent agreement between the computed theoretical and experimental elastic moduli, micro-harness and Poisson's ratio was achieved for majority of samples.  相似文献   
6.
As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function.  相似文献   
7.
Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.  相似文献   
8.
在深水压井循环期间,随着压井液的循环,井筒瞬态温度场不断变化,导致环空多相流动行为变化复杂,进而影响压井过程中的井筒压力分布。为快速准确地预测深水压井过程中不同循环时间和压井排量下的井筒瞬态温度分布,基于能量守恒原理,综合考虑压井液、钻杆、环空、地层、海水以及隔水管之间的热传递,建立了深水压井过程中井筒瞬态温度场解析模型。结合深水压井井筒瞬态传热特征,模拟分析了深水工程师法压井循环期间的井筒压力演变规律以及环空多相流动行为。分析结果表明:深水压井工况下,环空压井液循环温度与静温剖面相差较大,随着循环时间的延长和排量的增加,环空压井液循环温度逐渐偏离静温剖面;压井液温度的变化进一步影响环空自由气体体积波动,导致环空多相流动行为复杂多变。研究结果可为深水压井设计和现场作业提供理论支撑。  相似文献   
9.
Polyvinylidene fluoride (PVDF) has several crystal forms of which the α-form is nonpolar, while the β-form is polar and has the highest piezoelectric constant. α PVDF, when stretched, transforms into the β form, which has wide applications in sensors and actuators. Steered molecular dynamics simulations are used to study the transformation of a single chain of PVDF from a trans–gauche conformation to an all trans one. The Helmholtz free energy change (∆F) is estimated using Jarzynski's equality. The transformation starts at the chain ends followed by the transformation of the remaining chain. The free energy change for the transformation is found to be always positive, indicating that the TGTG' form has higher thermodynamic stability than the all trans form throughout the studied temperature range. With increasing temperature, free energy change for the transformation increases monotonically.  相似文献   
10.
The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.  相似文献   
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