全文获取类型
收费全文 | 35992篇 |
免费 | 2528篇 |
国内免费 | 2041篇 |
专业分类
电工技术 | 1240篇 |
综合类 | 1960篇 |
化学工业 | 12274篇 |
金属工艺 | 3573篇 |
机械仪表 | 961篇 |
建筑科学 | 2959篇 |
矿业工程 | 485篇 |
能源动力 | 1093篇 |
轻工业 | 1512篇 |
水利工程 | 96篇 |
石油天然气 | 1250篇 |
武器工业 | 293篇 |
无线电 | 3182篇 |
一般工业技术 | 5129篇 |
冶金工业 | 1411篇 |
原子能技术 | 662篇 |
自动化技术 | 2481篇 |
出版年
2024年 | 90篇 |
2023年 | 499篇 |
2022年 | 1157篇 |
2021年 | 1175篇 |
2020年 | 958篇 |
2019年 | 859篇 |
2018年 | 734篇 |
2017年 | 1002篇 |
2016年 | 1265篇 |
2015年 | 1228篇 |
2014年 | 1675篇 |
2013年 | 1872篇 |
2012年 | 2079篇 |
2011年 | 2734篇 |
2010年 | 1992篇 |
2009年 | 2464篇 |
2008年 | 1912篇 |
2007年 | 2375篇 |
2006年 | 2207篇 |
2005年 | 1763篇 |
2004年 | 1471篇 |
2003年 | 1480篇 |
2002年 | 1202篇 |
2001年 | 931篇 |
2000年 | 846篇 |
1999年 | 686篇 |
1998年 | 526篇 |
1997年 | 372篇 |
1996年 | 340篇 |
1995年 | 281篇 |
1994年 | 256篇 |
1993年 | 226篇 |
1992年 | 204篇 |
1991年 | 172篇 |
1990年 | 149篇 |
1989年 | 116篇 |
1988年 | 92篇 |
1987年 | 94篇 |
1986年 | 106篇 |
1985年 | 103篇 |
1984年 | 90篇 |
1983年 | 76篇 |
1982年 | 76篇 |
1981年 | 85篇 |
1980年 | 77篇 |
1978年 | 72篇 |
1977年 | 73篇 |
1976年 | 88篇 |
1975年 | 86篇 |
1974年 | 70篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
Masahiro Sato Miyu Koriyama Satoshi Watanabe Masato Ohtsuka Takayuki Sakurai Emi Inada Issei Saitoh Shingo Nakamura Kazuchika Miyoshi 《International journal of molecular sciences》2015,16(8):17838-17856
Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B4 (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types. 相似文献
12.
Nicholas Caffes David B. Kurland Volodymyr Gerzanich J. Marc Simard 《International journal of molecular sciences》2015,16(3):4973-4984
Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial KATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. 相似文献
13.
14.
Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC50 value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity. 相似文献
15.
本实验采用4D-非标记蛋白质组学技术研究秦川牛肉贮藏过程中(0~8 d)肌红蛋白含量及其衍生物的转化情况,阐释冷却秦川牛肉中肌红蛋白含量及其衍生物转化的分子机制。结果表明:贮藏过程中,肌红蛋白表达量在宰后0~4 d上升、4~8 d下降,利用非标记蛋白质组学技术鉴定出与肌红蛋白及其衍生物相关的差异蛋白14 种,具体包括代谢酶、氧化还原酶、过氧化物酶、伴侣蛋白4 类,这4 类蛋白的表达共同调控贮藏过程中肌红蛋白含量的变化及其3 种衍生物之间的转化,具体表现为贮藏过程中肌红蛋白表达量整体呈下降趋势,氧合肌红蛋白相对含量持续下降,脱氧肌红蛋白、高铁肌红蛋白相对含量逐渐增加,导致肉色发生褐变。本研究结果有利于理解秦川牛肉贮藏过程肉类变色的复杂生化变化机制。 相似文献
16.
17.
Qiang Liu Xinyu Mao Xiaoying Li Penghui Chen Xin Liu Ziyu Liu Danyang Zhu Haohong Chen Tengfei Xie Jiang Li 《Journal of the American Ceramic Society》2021,104(10):4927-4931
0.5 at.% Cr:ZnGa2O4 precursor was synthesized by the co-precipitation method with nitrates as raw materials, using ammonium carbonate as the precipitant. Low-agglomerated Cr:ZnGa2O4 powders with an average particle size of 43 nm were obtained by calcining the precursor at 900℃ for 4 h. Using the powders as starting materials, 0.5 at.% Cr:ZnGa2O4 ceramics with an average grain size of about 515 nm were prepared by presintering at 1150℃ for 5 h in air and HIP post-treatment at 1100℃ for 3 h under 200 MPa Ar. The in-line transmittance of 0.5 at.% Cr:ZnGa2O4 ceramics with a thickness of 1.3 mm reaches 59.5% at the wavelength of 700 nm. The Cr:ZnGa2O4 ceramics can be effectively excited by visible light and produce persistent luminescence at 700 nm. For Cr:ZnGa2O4 transparent ceramics, the brightness of afterglow was larger than 0.32 mcd/m2 after 30 min, which is far superior to that of Cr:ZnGa2O4 persistent luminescence powders. 相似文献
18.
Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
19.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
20.
This research is concerned with the problem of 4 degrees of freedom (DOF) ship manoeuvring identification modelling with the full-scale trial data. To avoid the multi-innovation matrix inversion in the conventional multi-innovation least squares (MILS) algorithm, a new transformed multi-innovation least squares (TMILS) algorithm is first developed by virtue of the coupling identification concept. And much effort is made to guarantee the uniformly ultimate convergence. Furthermore, the auto-constructed TMILS scheme is derived for the ship manoeuvring motion identification by combination with a statistic index. Comparing with the existing results, the proposed scheme has the significant computational advantage and is able to estimate the model structure. The illustrative examples demonstrate the effectiveness of the proposed algorithm, especially including the identification application with full-scale trial data. 相似文献