全文获取类型
收费全文 | 390227篇 |
免费 | 48753篇 |
国内免费 | 39193篇 |
专业分类
电工技术 | 31211篇 |
技术理论 | 17篇 |
综合类 | 34258篇 |
化学工业 | 66950篇 |
金属工艺 | 21741篇 |
机械仪表 | 25187篇 |
建筑科学 | 23514篇 |
矿业工程 | 8384篇 |
能源动力 | 13487篇 |
轻工业 | 22964篇 |
水利工程 | 11467篇 |
石油天然气 | 13631篇 |
武器工业 | 4378篇 |
无线电 | 47183篇 |
一般工业技术 | 45514篇 |
冶金工业 | 11230篇 |
原子能技术 | 5581篇 |
自动化技术 | 91476篇 |
出版年
2024年 | 857篇 |
2023年 | 5980篇 |
2022年 | 9880篇 |
2021年 | 13555篇 |
2020年 | 13149篇 |
2019年 | 11783篇 |
2018年 | 11003篇 |
2017年 | 14362篇 |
2016年 | 16339篇 |
2015年 | 18197篇 |
2014年 | 21536篇 |
2013年 | 25350篇 |
2012年 | 28439篇 |
2011年 | 33477篇 |
2010年 | 25102篇 |
2009年 | 25865篇 |
2008年 | 26112篇 |
2007年 | 29013篇 |
2006年 | 26160篇 |
2005年 | 22737篇 |
2004年 | 18923篇 |
2003年 | 15836篇 |
2002年 | 12399篇 |
2001年 | 9197篇 |
2000年 | 7655篇 |
1999年 | 6203篇 |
1998年 | 5031篇 |
1997年 | 4058篇 |
1996年 | 3665篇 |
1995年 | 3178篇 |
1994年 | 2771篇 |
1993年 | 2026篇 |
1992年 | 1654篇 |
1991年 | 1302篇 |
1990年 | 1057篇 |
1989年 | 844篇 |
1988年 | 599篇 |
1987年 | 389篇 |
1986年 | 378篇 |
1985年 | 388篇 |
1984年 | 347篇 |
1983年 | 233篇 |
1982年 | 314篇 |
1981年 | 188篇 |
1980年 | 188篇 |
1979年 | 106篇 |
1978年 | 49篇 |
1977年 | 54篇 |
1976年 | 33篇 |
1959年 | 37篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Vilde Yuli Stenberg Roy Hartvig Larsen Li-Wei Ma Qian Peng Petras Juzenas
yvind Sverre Bruland Asta Juzeniene 《International journal of molecular sciences》2021,22(9)
Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001. 相似文献
72.
So Young Kim Cheol Park Min Yeong Kim Seon Yeong Ji Hyun Hwangbo Hyesook Lee Su Hyun Hong Min Ho Han Jin-Woo Jeong Gi-Young Kim Chang-Gue Son JaeHun Cheong Yung Hyun Choi 《International journal of molecular sciences》2021,22(9)
Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC. 相似文献
73.
Tomasz Pdzinski Katarzyna Grzyb Konrad Skotnicki Piotr Filipiak Krzysztof Bobrowski Chryssostomos Chatgilialoglu Bronislaw Marciniak 《International journal of molecular sciences》2021,22(9)
Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO•) play an important role, being the most aggressive towards biomolecules. The reactions of HO• with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO• generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HO•, and by CB triplets allowed for assigning transient species to the pathways of products formation. 相似文献
74.
Rikako Tabata SungGi Chi Junichiro Yuda Yosuke Minami 《International journal of molecular sciences》2021,22(4)
Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence. 相似文献
75.
Meiling Shi Leqi Yao Junfeng Xu Chao Liang Yan Dong Qiyue Shao 《Journal of the American Ceramic Society》2021,104(7):3279-3288
Phosphors-converted LEDs (pc-LEDs) are excellent artificial light sources for indoor plant cultivation, in which the far-red-emitting component (700−780 nm) plays an important role in regulating the photomorphogenesis of plants. Accordingly, highly efficient and thermally stable far-red-emitting phosphors are indispensable for developing high-performance plant cultivation pc-LEDs. Herein, far-red-emitting YAl3(BO3)4:Cr3+ (YAB:Cr3+) phosphors were synthesized by solid-state reaction, and their photoluminescence characteristics, thermal quenching, quantum yield (QY), and application in pc-LEDs were systematically investigated. The YAB:Cr3+ phosphor has an intense broadband absorption to the blue light, simultaneously exhibiting the sharp-line 2E emission and the broadband 4 T2 emission of Cr3+ with a QY of ~86.7%. The far-red broadband emissions of YAB:Cr3+ centered at ~735 nm show a high resemblance to the active-state (PFR) absorption of plant phytochrome. Moreover, the YAB:Cr3+ phosphor shows the thermally enhanced luminescence at temperatures of 303−393 K and the near-zero thermal quenching up to 423 K. The anomalous thermal enhancement is attributed to the temperature-dependent repopulation between 2E and 4 T2 states. Finally, a pc-LED device was fabricated with the YAB:Cr3+ phosphor and blue chip, exhibiting the light out power of ~50.6 mW and energy conversion efficiency of ~17.4% at 100 mA drive current, respectively. The exceptional PL features including suitable excitation/emission wavelengths, suppressed thermal quenching and high QY make YAB:Cr3+ phosphors very promising for applications in plant growth pc-LEDs. 相似文献
76.
Maxim Stolyarchuk Julie Ledoux Elodie Maignant Alain Trouv Luba Tchertanov 《International journal of molecular sciences》2021,22(2)
Redox (reduction–oxidation) reactions control many important biological processes in all organisms, both prokaryotes and eukaryotes. This reaction is usually accomplished by canonical disulphide-based pathways involving a donor enzyme that reduces the oxidised cysteine residues of a target protein, resulting in the cleavage of its disulphide bonds. Focusing on human vitamin K epoxide reductase (hVKORC1) as a target and on four redoxins (protein disulphide isomerase (PDI), endoplasmic reticulum oxidoreductase (ERp18), thioredoxin-related transmembrane protein 1 (Tmx1) and thioredoxin-related transmembrane protein 4 (Tmx4)) as the most probable reducers of VKORC1, a comparative in-silico analysis that concentrates on the similarity and divergence of redoxins in their sequence, secondary and tertiary structure, dynamics, intraprotein interactions and composition of the surface exposed to the target is provided. Similarly, hVKORC1 is analysed in its native state, where two pairs of cysteine residues are covalently linked, forming two disulphide bridges, as a target for Trx-fold proteins. Such analysis is used to derive the putative recognition/binding sites on each isolated protein, and PDI is suggested as the most probable hVKORC1 partner. By probing the alternative orientation of PDI with respect to hVKORC1, the functionally related noncovalent complex formed by hVKORC1 and PDI was found, which is proposed to be a first precursor to probe thiol–disulphide exchange reactions between PDI and hVKORC1. 相似文献
77.
Dr. Thomas Le Bihan Dr. Cathryn H. S. Driver Dr. Thomas Ebenhan Dr. Nathalie Le Bris Dr. Jan Rijn Zeevaart Prof. Dr. Raphaël Tripier 《ChemMedChem》2021,16(5):809-821
An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu-GluCAB-2Mal and previous-generation [64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu-GluCAB-2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64Cu]Cu-Glu-CAB-2Mal. 相似文献
78.
Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis. 相似文献
79.
Nirupaplava Metta Rohit Ramachandran Marianthi Ierapetritou 《American Institute of Chemical Engineers》2021,67(2):e17095
Identification of feasible region of operations in multivariate processes is a problem of interest in several fields. This is particularly challenging when the process model is black-box in nature and/or is computationally expensive, as analytical solutions are not available and the number of possible model evaluations is limited. An efficient methodology is required to identify samples where the model is evaluated for developing a computationally efficient surrogate model. In this work, an artificial neural network based surrogate model is proposed which is integrated with a statistical-based approach (Jack-knifing) to estimate the variance of the surrogate model prediction. This allows implementation of an adaptive sampling approach where new samples are identified close to the feasible region boundary or in regions of high prediction uncertainty. The proposed approach performs better than a previously published kriging based method for different dimensionality case studies. 相似文献
80.
为了建立一种准确性高、成本低的植物油中苯并(a)芘测定的样品前处理方法,基于GB 5009.7—2016以自制氧化铝柱为固相萃取柱,采用单因素试验对称样量、洗脱剂量、洗脱流速、吸附剂存放时间、吸附剂量这5个影响植物油中苯并(a)芘洗脱的因素进行研究,优化前处理条件,并对测定方法进行考察。结果表明:优化的前处理条件为称样量0.100 0 g、洗脱剂量120 mL、吸附剂(氧化铝)量22 g、洗脱流速1滴/2 s、吸附剂存放时间少于12周;方法检出限为0.2 μg/L,样品加标回收率为94.23%~100.00%,RSD为1.20%~7.36%;同一样品测定结果与SGS测定值接近,相对平均偏差为2.36%~3.50%。说明本试验方法测定结果准确,可应用于油脂企业植物油中痕量苯并(a)芘的测定。 相似文献