全文获取类型
收费全文 | 8987篇 |
免费 | 892篇 |
国内免费 | 34篇 |
学科分类
工业技术 | 9913篇 |
出版年
2023年 | 110篇 |
2022年 | 73篇 |
2021年 | 268篇 |
2020年 | 231篇 |
2019年 | 276篇 |
2018年 | 298篇 |
2017年 | 324篇 |
2016年 | 402篇 |
2015年 | 341篇 |
2014年 | 462篇 |
2013年 | 657篇 |
2012年 | 637篇 |
2011年 | 776篇 |
2010年 | 592篇 |
2009年 | 604篇 |
2008年 | 530篇 |
2007年 | 394篇 |
2006年 | 364篇 |
2005年 | 313篇 |
2004年 | 247篇 |
2003年 | 249篇 |
2002年 | 225篇 |
2001年 | 192篇 |
2000年 | 152篇 |
1999年 | 140篇 |
1998年 | 209篇 |
1997年 | 163篇 |
1996年 | 136篇 |
1995年 | 92篇 |
1994年 | 55篇 |
1993年 | 64篇 |
1992年 | 41篇 |
1991年 | 45篇 |
1990年 | 44篇 |
1989年 | 41篇 |
1988年 | 21篇 |
1987年 | 18篇 |
1986年 | 15篇 |
1985年 | 18篇 |
1984年 | 9篇 |
1983年 | 9篇 |
1982年 | 5篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 7篇 |
1976年 | 12篇 |
1975年 | 8篇 |
1973年 | 4篇 |
1967年 | 5篇 |
排序方式: 共有9913条查询结果,搜索用时 15 毫秒
1.
Shraddha Parate Vikas Kumar Danishuddin Jong Chan Hong Keun Woo Lee 《International journal of molecular sciences》2021,22(10)
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
2.
Suk-Young Song Soonil Pyo Sungchul Choi Hee Sang Oh Jung Hwa Seo Ji Hea Yu Ahreum Baek Yoon-Kyum Shin Hoo Young Lee Ja Young Choi Sung-Rae Cho 《International journal of molecular sciences》2021,22(7)
Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O2 hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Cav 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Cav 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Cav 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE. 相似文献
3.
Yuria Jang Hong Moon Sohn Young Jong Ko Hoon Hyun Wonbong Lim 《International journal of molecular sciences》2021,22(1)
Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments. 相似文献
4.
5.
6.
Lee Dong-hun Jang Jae-il Kim Young-Ho 《Journal of Materials Science: Materials in Electronics》2022,33(14):11002-11016
Journal of Materials Science: Materials in Electronics - Solder joints of Au-20wt%Sn (Au-20Sn) between real light-emitting diode Si chips and AlN substrates were fabricated using thermo-compression... 相似文献
7.
Wonje Jang Junhyuk Hyun Jhonghyun An Minho Cho Euntai Kim 《IEEE/CAA Journal of Automatica Sinica》2022,9(1):187-204
The essential requirement for precise localization of a self-driving car is a lane-level map which includes road markings (RMs). Obviously, we can build the lane-level map by running a mobile mapping system (MMS) which is equipped with a high-end 3D LiDAR and a number of high-cost sensors. This approach, however, is highly expensive and ineffective since a single high-end MMS must visit every place for mapping. In this paper, a lane-level RM mapping system using a monocular camera is developed. The developed system can be considered as an alternative to expensive high-end MMS. The developed RM map includes the information of road lanes (RLs) and symbolic road markings (SRMs). First, to build a lane-level RM map, the RMs are segmented at pixel level through the deep learning network. The network is named RMNet. The segmented RMs are then gathered to build a lane-level RM map. Second, the lane-level map is improved through loop-closure detection and graph optimization. To train the RMNet and build a lane-level RM map, a new dataset named SeRM set is developed. The set is a large dataset for lane-level RM mapping and it includes a total of 25157 pixel-wise annotated images and 21000 position labeled images. Finally, the proposed lane-level map building method is applied to SeRM set and its validity is demonstrated through experimentation. 相似文献
8.
Dr. Ala Jo Mingi Kim Dr. Jong In Kim Jaeyoung Ha Yoon Soo Hwang Hyunsung Nam Dr. Injae Hwang Dr. Jae Bum Kim Prof. Seung Bum Park 《ChemMedChem》2021,16(7):1104-1115
Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities. 相似文献
9.
Jang Hye Ji Kim Jong Ha Lee Hyun-Sook Paik Hyun-Dong 《Food science and biotechnology》2022,31(6):731-737
Food Science and Biotechnology - The objective of this study was to develop a non-fermented probiotic milk that maintains its physicochemical properties, microbial properties, antioxidant activity,... 相似文献
10.
Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer. 相似文献