全文获取类型
收费全文 | 2348篇 |
免费 | 171篇 |
国内免费 | 1篇 |
专业分类
电工技术 | 7篇 |
化学工业 | 1055篇 |
金属工艺 | 21篇 |
机械仪表 | 41篇 |
建筑科学 | 77篇 |
矿业工程 | 5篇 |
能源动力 | 41篇 |
轻工业 | 565篇 |
水利工程 | 15篇 |
石油天然气 | 7篇 |
无线电 | 80篇 |
一般工业技术 | 293篇 |
冶金工业 | 71篇 |
原子能技术 | 6篇 |
自动化技术 | 236篇 |
出版年
2024年 | 5篇 |
2023年 | 48篇 |
2022年 | 276篇 |
2021年 | 306篇 |
2020年 | 84篇 |
2019年 | 70篇 |
2018年 | 88篇 |
2017年 | 84篇 |
2016年 | 98篇 |
2015年 | 75篇 |
2014年 | 95篇 |
2013年 | 157篇 |
2012年 | 137篇 |
2011年 | 163篇 |
2010年 | 109篇 |
2009年 | 117篇 |
2008年 | 92篇 |
2007年 | 92篇 |
2006年 | 76篇 |
2005年 | 62篇 |
2004年 | 54篇 |
2003年 | 42篇 |
2002年 | 29篇 |
2001年 | 22篇 |
2000年 | 14篇 |
1999年 | 6篇 |
1998年 | 19篇 |
1997年 | 13篇 |
1996年 | 15篇 |
1995年 | 13篇 |
1994年 | 5篇 |
1993年 | 8篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1980年 | 1篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1934年 | 1篇 |
1933年 | 1篇 |
1932年 | 2篇 |
排序方式: 共有2520条查询结果,搜索用时 15 毫秒
91.
Dr. Andrea Angeli Prof. Marta Ferraroni Prof. Antonella Capperucci Dr. Damiano Tanini Prof. Gabriele Costantino Prof. Claudiu T. Supuran 《ChemMedChem》2022,17(11):e202200085
A study on the activity of selenocarbamates as a novel chemotype acting as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors is reported. Undergoing CA-mediated hydrolysis, selenocarbamates release selenolates behaving as zinc binding groups and effectively inhibiting CAs. A series of selenocarbamates characterised by high molecular diversity and complexity have been studied against different human CA isoforms such as hCA I, II, IX and XII. Selenocarbamates behave as masked selenols with potential biological applications as prodrugs for CAs inhibition-based strategies. X-ray studies provided insights into the binding mode of this novel class of CA inhibitors. 相似文献
92.
93.
94.
Federica Barbagallo Sandro La Vignera Rossella Cannarella Laura M. Mongioì Vincenzo Garofalo Claudia Leanza Marta Marino Aldo E. Calogero Rosita A. Condorelli 《International journal of molecular sciences》2022,23(2)
Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years. 相似文献
95.
Chiara Cipollina Andreina Bruno Salvatore Fasola Marta Cristaldi Bernardo Patella Rosalinda Inguanta Antonio Vilasi Giuseppe Aiello Stefania La Grutta Claudia Torino Elisabetta Pace 《International journal of molecular sciences》2022,23(3)
Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds. 相似文献
96.
Marta Gabasa Marselina Arshakyan Alejandro Llorente Lourdes Chuli-Peris Irina Pavelescu Antoni Xaubet Javier Pereda Jordi Alcaraz 《International journal of molecular sciences》2020,21(22)
Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair. 相似文献
97.
Elzbieta Pawluczuk Marta ukaszewicz-Zajc Barbara Mroczko 《International journal of molecular sciences》2020,21(22)
Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC. 相似文献
98.
Carmen J. Pastor-Maldonado Juan M. Surez-Rivero Suleva Povea-Cabello Mnica lvarez-Crdoba Irene Villaln-García Manuel Munuera-Cabeza Alejandra Surez-Carrillo Marta Talavern-Rey Jos A. Snchez-Alczar 《International journal of molecular sciences》2020,21(22)
The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review. 相似文献
99.
Izabela Mauch Oktawian Stachurski Paulina Kosikowska-Adamus Marta Makowska Marta Bauer Dariusz Wyrzykowski Aleksandra Ha Wojciech Kamysz Milena Deptua Micha Pikua Emilia Sikorska 《International journal of molecular sciences》2020,21(23)
Antimicrobial peptides (AMPs) constitute a promising tool in the development of novel therapeutic agents useful in a wide range of bacterial and fungal infections. Among the modifications improving pharmacokinetic and pharmacodynamic characteristics of natural AMPs, an important role is played by lipidation. This study focuses on the newly designed and synthesized lipopeptides containing multiple Lys residues or their shorter homologues with palmitic acid (C16) attached to the side chain of a residue located in the center of the peptide sequence. The approach resulted in the development of lipopeptides representing a model of surfactants with two polar headgroups. The aim of this study is to explain how variations in the length of the peptide chain or the hydrocarbon side chain of an amino acid residue modified with C16, affect biological functions of lipopeptides, their self-assembling propensity, and their mode of action. 相似文献
100.
Marta Vallverdú-Prats Ramon Brugada Mireia Alcalde 《International journal of molecular sciences》2022,23(2)
Arrhythmogenic cardiomyopathy is a heritable heart disease associated with desmosomal mutations, especially premature termination codon (PTC) variants. It is known that PTC triggers the nonsense-mediated decay (NMD) mechanism. It is also accepted that PTC in the last exon escapes NMD; however, the mechanisms involving NMD escaping in 5′-PTC, such as reinitiation of translation, are less known. The main objective of the present study is to evaluate the likelihood that desmosomal genes carrying 5′-PTC will trigger reinitiation. HL1 cell lines were edited by CRISPR/Cas9 to generate isogenic clones carrying 5′-PTC for each of the five desmosomal genes. The genomic context of the ATG in-frame in the 5′ region of desmosomal genes was evaluated by in silico predictions. The expression levels of the edited genes were assessed by Western blot and real-time PCR. Our results indicate that the 5′-PTC in PKP2, DSG2 and DSC2 acts as a null allele with no expression, whereas in the DSP and JUP gene, N-truncated protein is expressed. In concordance with this, the genomic context of the 5′-region of DSP and JUP presents an ATG in-frame with an optimal context for the reinitiation of translation. Thus, 5′-PTC triggers NMD in the PKP2, DSG2* and DSC2 genes, whereas it may escape NMD through the reinitiation of the translation in DSP and JUP genes, with no major effects on ACM-related gene expression. 相似文献