首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   56246篇
  免费   6068篇
  国内免费   1862篇
电工技术   2428篇
技术理论   2篇
综合类   3060篇
化学工业   10787篇
金属工艺   2146篇
机械仪表   1644篇
建筑科学   3688篇
矿业工程   1793篇
能源动力   1070篇
轻工业   11601篇
水利工程   1293篇
石油天然气   1583篇
武器工业   276篇
无线电   5083篇
一般工业技术   5925篇
冶金工业   3774篇
原子能技术   665篇
自动化技术   7358篇
  2024年   75篇
  2023年   1181篇
  2022年   2324篇
  2021年   3654篇
  2020年   2243篇
  2019年   2179篇
  2018年   2257篇
  2017年   1891篇
  2016年   2701篇
  2015年   3228篇
  2014年   3798篇
  2013年   4118篇
  2012年   3556篇
  2011年   2819篇
  2010年   2248篇
  2009年   2192篇
  2008年   2313篇
  2007年   3563篇
  2006年   3742篇
  2005年   3217篇
  2004年   2127篇
  2003年   1981篇
  2002年   1362篇
  2001年   801篇
  2000年   513篇
  1999年   464篇
  1998年   260篇
  1997年   225篇
  1996年   286篇
  1995年   260篇
  1994年   290篇
  1993年   196篇
  1992年   187篇
  1991年   183篇
  1990年   178篇
  1989年   132篇
  1988年   96篇
  1987年   97篇
  1986年   96篇
  1985年   101篇
  1984年   102篇
  1983年   81篇
  1982年   75篇
  1981年   67篇
  1980年   63篇
  1979年   39篇
  1975年   39篇
  1964年   48篇
  1962年   71篇
  1955年   45篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
推导陈垃圾在滚筒筛中的运动方程并求数值解,按最大位置角将陈垃圾运动模式划分成滚落、抛落、圆周运动,给出不同筛筒转速、半径、动摩擦因数下的运动模式判别云图. 滚筒筛试验结果显示,陈垃圾运动的最大位置角随转速的升高先增大后不变,转速超过50 r/min后垃圾进行圆周运动. 陈垃圾滚筒筛的筛分效率随转速增大呈先升后降的趋势,随抛落差的增大呈持续上升的趋势,随着原料水的质量分数的增加呈下降的趋势. 基于试验结果,给出滚筒筛最优转速取值云图,在实际工程中可根据垃圾动摩擦因数及滚筒半径选择最优转速,同时减小水的质量分数以提高筛分效率.  相似文献   
2.
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   
3.
非口腔组织中的苦味受体(TAS2Rs)可能成为相关疾病治疗的新靶点。 该研究将表达有 TAS2Rs 的细胞作为敏感元 件,根据其生理特性与不同的传感器耦合,探究了味觉受体异位表达及其在个性化药物筛选中的应用,构建了针对不同疾病模 型的个性化药物筛选平台。 首先,基于细胞阻抗传感器以及内源性表达 TAS2R38 受体的结肠癌细胞,开发了异硫氰酸酯类物 质特异性药物筛选平台,求得苯硫脲的 EC50 为 157. 6 μM;其次,结合微电极阵列检测系统,探究了 TAS2Rs 激动剂地芬尼多 (5~ 160 μM)和水杨苷(0. 001~ 100 μM)对心肌细胞收缩的抑制作用;此外,基于 3D 呼吸道平滑肌细胞 (ASMCs) 阵列,结合凝 胶成像系统,探究了 TAS2Rs 激动剂桔皮素(20 μM)对呼吸道平滑肌细胞的舒张作用。  相似文献   
4.
5.
Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.  相似文献   
6.
The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.  相似文献   
7.
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.  相似文献   
8.
In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.  相似文献   
9.
Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.  相似文献   
10.
为解决基于视频流的人体关键点检测效果不佳及视频流切片后可能会发生运动模糊的问题,提出了一种改进的RetinaNet-CPN网络对人体关键点进行检测,有效解决切片后运动模糊图像的干扰并提高了人体关键点的检测准确率.视频流切片后,先用改进的RetinaNet网络检测出图片中的所有人并对每个目标框做模糊检测,对大于阈值的目标框做去模糊处理,最后用引入注意力机制的CPN网络提取关键点.将RetinaNet衡量预测框与真实框差异的IOU函数改成DIOU后,在仿真实验中目标检测AP提高了近3%;对于模糊的图片,利用匀速直线运动频谱特征估算出的模糊核与实际模糊核相差不大,对其做去模糊处理后基本能恢复出原清晰图片;同时引入注意力机制为各通道和特征层分配合理的权重,使得CPN检测AP提高近1%,AR提升0.5%.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号