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31.
Ying Yang Hui-Yun Chen Hua Hao Ke-Jian Wang 《International journal of molecular sciences》2022,23(10)
Scyreprocin is an antimicrobial peptide first identified in the mud crab Scylla paramamosain. Herein, we showed that its recombinant product (rScyreprocin) could significantly inhibit the growth of human lung cancer NCI-H460 cells (H460), but showed no cytotoxicity to human lung fibroblasts (HFL1). rScyreprocin was a membrane-active peptide that firstly induced the generation of reactive oxygen species (ROS) in H460, and led to endoplasmic reticulum stress and Ca2+ release, which resulted in mitochondrial dysfunction and subsequently activation of caspase-3 cascades, and ultimately led to apoptosis. The comprehensive results indicated that rScyreprocin exerted anticancer activity by disrupting cell membrane and inducing apoptosis. The in vivo efficacy test demonstrated that intratumoral injection of rScyreprocin significantly inhibited the growth of H460 xenografts, which was close to that of the cisplatin (inhibition rate: 69.94% vs. 80.76%). Therefore, rScyreprocin is expected to become a promising candidate for the treatment of lung cancer. 相似文献
32.
Sara Silva Kaido Kurrikoff Ülo Langel Antnio J. Almeida Nuno Vale 《International journal of molecular sciences》2022,23(15)
Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. 相似文献
33.
The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs. 相似文献
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35.
Lucas Weißenborn Elie Richel Helena Hüseman Julia Welzer Silvan Beck Simon Schfer Heinrich Sticht Klaus Überla Jutta Eichler 《International journal of molecular sciences》2022,23(11)
Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity. 相似文献
36.
37.
Miaomiao Jin Zhanxin Song Wei Liu Zilu Zhou Guozhen Wang Mo Xian 《International journal of molecular sciences》2022,23(14)
Biological self-assembly procedures, which are generally carried out in an aqueous solution, have been found to be the most promising method for directing the fabrication of diverse nanothermites, including Al/CuO nanothermite. However, the aqueous environment in which Al nanoparticles self-assemble has an impact on their stability. We show that using a peptide to self-assemble Al or CuO nanoparticles considerably improves their durability in phosphate buffer aqueous solution, with Al and CuO nanoparticles remaining intact in aqueous solution for over 2 weeks with minimal changes in the structure. When peptide-assembled Al/CuO nanothermite was compared with a physically mixed sample in phosphate buffer for 30 min, the energy release of the former was higher by 26%. Furthermore, the energy release of peptide-assembled Al/CuO nanocomposite in phosphate buffer showed a 6% reduction by Day 7, while that of the peptide-assembled Al/CuO nanocomposite in ultrapure water was reduced by 75%. Taken together, our study provides an easy method for keeping the thermal activity of Al/CuO nanothermite assembled in aqueous solution. 相似文献
38.
本实验以藜麦蛋白为原料,采用碱性蛋白酶、复合蛋白酶、风味蛋白酶、木瓜蛋白酶、中性蛋白酶分别对藜麦蛋白进行水解,制备藜麦蛋白肽。通过单因素实验对五种酶水解制备的藜麦蛋白肽以蛋白水解度、DPPH自由基清除能力、·OH自由基清除能力、ABTS+自由基清除能力、·O2-自由基清除能力为测定指标,研究五种蛋白酶对藜麦蛋白的水解能力和抗氧化活性影响,选出效果相对较佳的酶水解工艺。综合各指标的结果表明,碱性蛋白酶和复合蛋白酶水解能力较强,制备的藜麦蛋白肽抗氧化活性较其他两种酶更好。碱性蛋白酶和复合蛋白酶最佳酶解工艺分别为:酶与底物比0.5%(w/w),底物与水为1∶25(w/v),水解温度50℃,水解时间5h,pH10.0;酶与底物比0.5%(w/w),底物与水为1∶25(w/v),水解温度55℃,水解时间5h,pH8.0。本研究为藜麦蛋白的后期的深加工利用提供一定理论依据。 相似文献
39.
Enrico Mario Alessandro Fassi Mariangela Garofalo Jacopo Sgrignani Michele Dei Cas Matteo Mori Gabriella Roda Andrea Cavalli Giovanni Grazioso 《International journal of molecular sciences》2022,23(9)
(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and Kd values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules. 相似文献
40.