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81.
Guadalupe Rosario Fajardo-Ordua Edgar Ledesma-Martínez Itzen Aguiiga-Snchez María de Lourdes Mora-García Benny Weiss-Steider Edelmiro Santiago-Osorio 《International journal of molecular sciences》2021,22(9)
Acute myeloid leukemia (AML), the most common type of leukemia in older adults, is a heterogeneous disease that originates from the clonal expansion of undifferentiated hematopoietic progenitor cells. These cells present a remarkable variety of genes and proteins with altered expression and function. Despite significant advances in understanding the molecular panorama of AML and the development of therapies that target mutations, survival has not improved significantly, and the therapy standard is still based on highly toxic chemotherapy, which includes cytarabine (Ara-C) and allogeneic hematopoietic cell transplantation. Approximately 60% of AML patients respond favorably to these treatments and go into complete remission; however, most eventually relapse, develop refractory disease or chemoresistance, and do not survive for more than five years. Therefore, drug resistance that initially occurs in leukemic cells (primary resistance) or that develops during or after treatment (acquired resistance) has become the main obstacle to AML treatment. In this work, the main molecules responsible for generating chemoresistance to Ara-C in AML are discussed, as well as some of the newer strategies to overcome it, such as the inclusion of molecules that can induce synergistic cytotoxicity with Ara-C (MNKI-8e, emodin, metformin and niclosamide), subtoxic concentrations of chemotherapy (PD0332991), and potently antineoplastic treatments that do not damage nonmalignant cells (heteronemin or hydroxyurea + azidothymidine). 相似文献
82.
Tomasz Z. Tomkiewicz Nuria Surez-Herrera Frans P. M. Cremers Rob W. J. Collin Alejandro Garanto 《International journal of molecular sciences》2021,22(9)
The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1. 相似文献
83.
Mootaz M. Salman Zaid Al-Obaidi Philip Kitchen Andrea Loreto Roslyn M. Bill Richard Wade-Martins 《International journal of molecular sciences》2021,22(9)
Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools. 相似文献
84.
Justyna Korczynska Aleksandra Czumaj Michal Chmielewski Julian Swierczynski Tomasz Sledzinski 《International journal of molecular sciences》2021,22(9)
Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk. 相似文献
85.
Helena Kratochvílov Milo Mrz Barbora J. Kasperov Daniel Hlav
ek Jakub Mahrík Ivana Lakov Anna Cinkajzlov Zdenk Matloch Zdeka Lacinov Jaroslava Trnovsk Peter Ivk Peter Novodvorský Ivan Netuka Martin Haluzík 《International journal of molecular sciences》2021,22(9)
The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis. 相似文献
86.
Ewa ya Katarzyna Dziendzikowska Dariusz Kamola Jacek Wilczak Rafa Sapierzyski Joanna Harasym Joanna Gromadzka-Ostrowska 《International journal of molecular sciences》2021,22(9)
Background: The incidence of Crohn’s disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient’s lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (colitis) in the early stages of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD in an animal model. Methods: Sprague–Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively. Results: Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of colitis. Conclusions: Dietary oat beta-glucans can reduce colitis at the molecular and organ level and accelerate CD remission. 相似文献
87.
Nuchanart Suealek Thipaporn Tharavanij Robert M. Hackman Carl L. Keen Roberta R. Holt Benjapun Burawat Ammara Chaikan Rattana Tiengtip Panadda Rojpibulstit 《European Journal of Lipid Science and Technology》2021,123(2):2000126
The potential cardiovascular benefit of virgin olive oil (VOO) is widely recognized. However, the use of VOO at very high cooking temperatures makes these oils poorly suited for many Asian dishes. The use of tea seed oil (TSO) is increasing in Thailand, with TSO having a higher smoke point than VOO. The current study examines the effects of daily TSO intake in healthy adults. In a randomized, single-blind crossover design, 12 men consumed for 3 weeks 40 g day−1 of food prepared with either TSO or VOO as a cooking oil. Plasma lipids, thiobarbituric acid reactive substances (TBARS), and oxidant defense enzyme activities are measured before and after each 3-week intervention period. Gas chromatography analysis of TSO and VOO demonstrates that both oils are equally high in monounsaturated fatty acid. The dietary incorporation of TSO and VOO for three weeks reduces low-density lipoprotein cholesterol (LDL-C) concentrations by 15% and 13%, respectively; with total cholesterol (TC) levels lowered by 10% in both groups. No significant changes in TBARS or antioxidant enzyme activity is observed. These results support the concept that Thai TSO can be utilized as a suitable and healthy alternative oil for high-temperature cooking in many Thai and Asian diets. Practical Applications: Tea seed oil from Camellia oleifera grown in Thailand has been recently reported to favorably lower lipid profiles in hamsters fed a high-fat diet in a manner similar to feeding refined olive oil or grapeseed oil. A pilot crossover trial is conducted to compare the effects of three weeks of daily intake of either TSO or VOO in healthy human adults. Consumption of both oils produced significant reductions in TC and LDL-C. Thai TSO leads to favorable lipid profiles and is a reasonable choice for many Thai and Asian food recipes. 相似文献
88.
指出普通中央空调在防范空气类传播疾病时 ,存有缺陷 ,必须采取有效措施 ,对其进行适当改进 ,以提高中央空调在使用中防范疾病传播的能力 相似文献
89.
目的筛选出口蹄疫病毒(FMDV)基因组上适于设计siRNA的基因片段。方法以FMDV WFL株RNA为模板,用3′RACE法扩增出2C-P3-3′NCR序列,将PCR扩增片段克隆到pMD18-T载体上,转化E.coli DH5α,筛选阳性重组子,进行序列测定,并与参考毒株序列比较。结果扩增的基因片段大小为4033bp,其2C、P3和3′NCR序列的核苷酸序列与参考毒株的同源性分别为87·11%~94·23%、84·91%~96·66%和66·98%~82·35%,2C和P3与参考毒株的氨基酸同源性分别为94·97%~99·39%和91·84%~98·55%,WFL株P3基因的第1150~1270、1680~1840和2080~2490bp以及2C基因的第354~470bp范围内与参考毒株具有高度保守的特性。因此,可以依据siRNA设计原则,在这4个区域内筛选抑制效果好的siRNA。结论成功克隆了FMDV WFL株2C-P3-3′NCR基因的序列,并筛选出4个适于设计siRNA的基因区段。 相似文献
90.
氰烯菌酯(JS399-19)防治水稻恶苗病的研究 总被引:6,自引:2,他引:6
氰烯菌酯(JS399-19)是一种结构新颖、作用方式独特的高效杀菌剂。离体抑菌活性测定表明,JS399-19对水稻恶苗病多菌灵敏感菌株和抗性菌株均有相似活性,EC50为0.1612~0.3136μg/mL,EC95为1.5387~6.0455μg/mL;持效性测定表明,JS399-19在10d内对恶苗病菌的抑菌率是稳定的,抑菌率为77.9%~81.4%;种子安全性试验表明,以25%JS399-19SC1:1000倍浸种处理对水稻种子的发芽势有一定的影响,但不影响发芽率、出苗率及成苗率,1:2000、1:3000、1:4000倍浸种处理时水稻种子的发芽势、发芽率、出苗率成苗率等均与空白对照无明显差异;温室小区筛选试验表明,当25%JS399-19SC1:500、1:1000、1:2000、1:3000浸种处理时30d防效均为100%,1:4000倍时防效大于92%;初步应用技术研究表明,JS399-19防治水稻恶苗病,浸种处理剂量为1:3000~4000倍,当浸种温度为15~20℃时,浸种时间以48~72h为宜。本研究为氰烯菌酯防治水稻恶苗病的应用开发提供了依据。 相似文献