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41.
Albena Momchilova Roumen Pankov Alexander Alexandrov Tania Markovska Stefan Pankov Plamen Krastev Galya Staneva Evgenia Vassileva Nikolai Krastev Adriana Pinkas 《International journal of molecular sciences》2022,23(14)
Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products—ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine. 相似文献
42.
本文介绍了一种基于多微处理器的主从式核物位监测系统的设计。简述了测量原理。从外部结构、硬件电路、通讯协议和软件编制几个方面详细介绍了系统设计。该系统目前在多个发电厂除尘系统得到应用,取得很好的效果。 相似文献
43.
提出了一种结合视觉Transformer和CNN的道路裂缝检测方法。利用CNN来捕获局部的细节信息,同时利用视觉Transformer来捕获全局特征。通过设计的Fusion特征融合模块将两者提取的特征有机地结合在一起,从而解决了单独使用CNN或视觉Transformer方法存在的局限。最终将结果传递至交互式解码器,生成道路裂缝的检测结果。实验结果表明,无论是在公开的数据集上还是在自建的数据集上,相较于单独使用CNN或视觉Transformer的方法,所提出的方法在道路裂缝检测任务中有更好的效果。 相似文献
44.
46.
Ichiro Kawahata David I. Finkelstein Kohji Fukunaga 《International journal of molecular sciences》2022,23(11)
α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the SNCA gene. Missense mutations and gene duplications in the SNCA gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. Consequently, this review focuses on the pathogenic impact of α-synuclein phosphorylation and its kinases during the neurodegeneration process in α-synucleinopathy. 相似文献
47.
Jonas Folke Emil Bergholt Bente Pakkenberg Susana Aznar Tomasz Brudek 《International journal of molecular sciences》2022,23(12)
Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-nAbs), which are important partakers in anti-aggregatory processes, immune-mediated clearance, and anti-inflammatory functions. To elaborate further on the timeline of autoimmune aberrancies towards αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-nAbs in serum samples from prodromal (p) phases of MSA and PD. Using an electrochemiluminescence competition immunoassay, we confirmed that the repertoire of high-affinity anti-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, leading to aggregation of the protein. Thus, this study provides novel insights into possible causes behind the pathogenesis in synucleinopathies such as MSA and PD. 相似文献
48.
Aigli G. Vakrakou Anastasia Alexaki Maria-Evgenia Brinia Maria Anagnostouli Leonidas Stefanis Panos Stathopoulos 《International journal of molecular sciences》2022,23(15)
This article recapitulates the evidence on the role of mammalian targets of rapamycin (mTOR) complex pathways in multiple sclerosis (MS). Key biological processes that intersect with mTOR signaling cascades include autophagy, inflammasome activation, innate (e.g., microglial) and adaptive (B and T cell) immune responses, and axonal and neuronal toxicity/degeneration. There is robust evidence that mTOR inhibitors, such as rapamycin, ameliorate the clinical course of the animal model of MS, experimental autoimmune encephalomyelitis (EAE). New, evolving data unravel mechanisms underlying the therapeutic effect on EAE, which include balance among T-effector and T-regulatory cells, and mTOR effects on myeloid cell function, polarization, and antigen presentation, with relevance to MS pathogenesis. Radiologic and preliminary clinical data from a phase 2 randomized, controlled trial of temsirolimus (a rapamycin analogue) in MS show moderate efficacy, with significant adverse effects. Large clinical trials of indirect mTOR inhibitors (metformin) in MS are lacking; however, a smaller prospective, non-randomized study shows some potentially promising radiological results in combination with ex vivo beneficial effects on immune cells that might warrant further investigation. Importantly, the study of mTOR pathway contributions to autoimmune inflammatory demyelination and multiple sclerosis illustrates the difficulties in the clinical application of animal model results. Nevertheless, it is not inconceivable that targeting metabolism in the future with cell-selective mTOR inhibitors (compared to the broad inhibitors tried to date) could be developed to improve efficacy and reduce side effects. 相似文献
49.
针对调控系统运行过程中出现的异常状态,提出基于粗糙熵加权密度的智能电网调控系统运行异常数据
检测方法。采用粗糙集对电网调控系统运行数据进行分析和推理;利用隶属度的割关系方法,将复杂的不确定关系
转化为布尔数据并排序;基于对象加权密度对智能电网调控系统运行中出现的异常数据进行检测,实现对调控系统
各种功能异常状态数据准确识别。采用真实电网调控系统数据对所提方法进行验证,结果表明:该方法与传统异常
状态识别方法相比,具有更高准确率和更低漏判率。 相似文献
50.
基于30个地区高校创新能力和人才创新指数,运用双变量相关性分析法,明确了高校创新能力对人才创新指数的25个关键影响因素。通过对25个关键影响因素的因子分析,提取了3个共性因子,分别为f1研发资源、f2创新平台建设、f3创新主体。采用多元回归法,探究3个共性因子对人才创新指数的显著性影响。研究发现,地区高校的研发资源是重要因素,一定程度上影响着创新人才培养质量。基于此,提出了三条建议:重点优化地区高校研发资源;完善高校创新平台;不断提高创新主体的创新思维与创新能力。研究成果为高校提高科技创新型人才的培养质量提供一定理论指导。 相似文献