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1.
Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM.  相似文献   
2.
Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.  相似文献   
3.
1 IntroductionIndesigningacomputercommunicationnet work ,thenetworkaveragedelayisanimportantpa rameterinthenetworkperformance .Inthispaper,weonlyconsiderM /M/1networks,whichmeansthatthemessageprocessingtimeisaprobabilisticdensityfunctionwithnegativepower,thegroupar rivalandsendingisofPoissiondistributionwithasinglequeue .Supposethatthenetworktopologicalstructureandtheestimatesoftheexternaltrafficrequirementsaregiven ,howtoselecttheoptimalroutestobeusedbythecommunicatingnodesinthenetworksoast…  相似文献   
4.
本文提出了一种抗非视线传播(Non-Line-of-Sight)干扰的TDOA定位算法。该算法采用退火与遗传算法相结合的方式,在满足给定条件的空间内搜索源点坐标值。数值仿真表明,该算法具备抗NLOS干扰的能力,与传统TDOA算法相比,该算法无需知道各基站的非视线传播干扰分布,是一种实用有效的定位算法。  相似文献   
5.
27例乙型血友病患者Ⅸ因子基因突变研究   总被引:1,自引:0,他引:1  
采用PCR(聚合酶链反应)及GAWTS(GenomicAmplificationwithTranscriptsSequencing)技术,研究了江苏、湖北、山东、广东、福建、宁夏六省区27例乙型血友病患者及其家系成员FⅨ(九因子)基因各2.2Kb DNA序列。在2l例中发现20种不同类型的突变。其中12种是未曾报道的新突变。38%的突变发生在CpG二核苷致序列上,进一步证实了CpG确系突变热点。同时检出6例女性为致病基因携带者。对开展基因产前诊断及优生优育等,具有重要意义。  相似文献   
6.
An integrated automatic test data generation system   总被引:3,自引:0,他引:3  
The Godzilla automatic test data generator is an integrated collection of tools that implements a relatively new test data generation method—constraint-based testing—that is based on mutation analysis. Constraint-based testing integrates mutation analysis with several other testing techniques, including statement coverage, branch coverage, domain perturbation, and symbolic evaluation. Because Godzilla uses a rule-based approach to generate test data, it is easily extendible to allow new testing techniques to be integrated into the current system. This article describes the system that has been built to implement constraint-based testing. Godzilla's design emphasizes orthogonality and modularity, allowing relatively easy extensions. Godzilla's internal structure and algorithms are described with emphasis on internal structures of the system and the engineering problems that were solved during the implementation.Parts of this research were supported by Contract F30602-85-C-0255 through Rome Air Development Center while the author was a graduate student at the Georgia Institute of Technology.  相似文献   
7.
建立了适用于大批量标本基因突变筛查的双脱氧指纹图谱法即ddF。该技术民测定DNA序列的双脱氧末端终止法及SSCP二者长处于一身,即只作一个双脱氧末端终止反应,然后将反应产物在与SSCP相同的电泳条件下进行聚丙烯酰胺凝胶电泳,这样有突变的样品不会漏检,阳性检出率高达100%。  相似文献   
8.
为克服粒子群算法容易陷入局部最优和全局寻优精度不高的缺点,通过对算法的局部寻优和全局寻优的特点进行分析,首先使用正态分布衰减策略改进惯性权重;同时基于算法运行的时间自适应采用不同的基于高斯分布及柯西分布的变异优化策略,解决全局搜索和局部开发能力的不平衡问题,实现了局部寻优和全局寻优的双重优化,满足了提高寻优速度和寻优精度的目的.为验证算法有效性及实用性,将改进算法用于预测新冠肺炎疫情传播情况.选取100天新冠肺炎疫情每日新确诊人数的数据,利用算法优化前馈神经网络的参数,使训练好的神经网络模型预测新冠肺炎疫情的性能提升.实验部分首先使用测试函数将改进的算法与其它五种算法进行对比,验证算法的良好性能,最后应用到神经网络完成新冠肺炎疫情传播预测.  相似文献   
9.
规约变异测试从软件功能的角度,对规约进行分析,从而揭示规约中存在的问题。本文提出一种基于UML状态图的变异测试方法,针对每种变异算子,分析其是否会引入冲突,进而有效避免不合理的变异操作;分析了每种变异算子产生等价变异体的条件,能够在生成变异体的同时检测并移除等价变异体,进而减少其对测试过程的影响;给出了杀掉每种变异体所需满足的条件,可在此基础上产生杀掉特定变异体所需的测试用例,从而提高测试用例集的质量。在此基础上,根据变异算子的实际功能,整合了功能相同的算子,减少了变异算子的数量,从而进一步降低了变异测试的开销。实验结果表明,本方法能够较好地提高测试用例的质量,进而提升测试的效率。  相似文献   
10.
Inhibition of the major human drug-metabolizing cytochrome P450 3A4 (CYP3A4) by pharmaceuticals and other xenobiotics could lead to toxicity, drug–drug interactions and other adverse effects, as well as pharmacoenhancement. Despite serious clinical implications, the structural basis and attributes required for the potent inhibition of CYP3A4 remain to be established. We utilized a rational inhibitor design to investigate the structure–activity relationships in the analogues of ritonavir, the most potent CYP3A4 inhibitor in clinical use. This study elucidated the optimal length of the head-group spacer using eleven (series V) analogues with the R1/R2 side-groups as phenyls or R1–phenyl/R2–indole/naphthalene in various stereo configurations. Spectral, functional and structural characterization of the inhibitory complexes showed that a one-atom head-group linker elongation, from pyridyl–ethyl to pyridyl–propyl, was beneficial and markedly improved Ks, IC50 and thermostability of CYP3A4. In contrast, a two-atom linker extension led to a multi-fold decrease in the binding and inhibitory strength, possibly due to spatial and/or conformational constraints. The lead compound, 3h, was among the best inhibitors designed so far and overall, the strongest binder (Ks and IC50 of 0.007 and 0.090 µM, respectively). 3h was the fourth structurally simpler inhibitor superior to ritonavir, which further demonstrates the power of our approach.  相似文献   
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