全文获取类型
收费全文 | 2049篇 |
免费 | 196篇 |
国内免费 | 2篇 |
专业分类
电工技术 | 8篇 |
综合类 | 1篇 |
化学工业 | 1224篇 |
金属工艺 | 33篇 |
机械仪表 | 24篇 |
建筑科学 | 58篇 |
矿业工程 | 11篇 |
能源动力 | 50篇 |
轻工业 | 411篇 |
水利工程 | 11篇 |
石油天然气 | 7篇 |
无线电 | 50篇 |
一般工业技术 | 230篇 |
冶金工业 | 30篇 |
原子能技术 | 1篇 |
自动化技术 | 98篇 |
出版年
2024年 | 4篇 |
2023年 | 49篇 |
2022年 | 315篇 |
2021年 | 416篇 |
2020年 | 94篇 |
2019年 | 94篇 |
2018年 | 90篇 |
2017年 | 104篇 |
2016年 | 128篇 |
2015年 | 85篇 |
2014年 | 113篇 |
2013年 | 124篇 |
2012年 | 108篇 |
2011年 | 95篇 |
2010年 | 59篇 |
2009年 | 73篇 |
2008年 | 59篇 |
2007年 | 50篇 |
2006年 | 40篇 |
2005年 | 31篇 |
2004年 | 31篇 |
2003年 | 19篇 |
2002年 | 11篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 2篇 |
排序方式: 共有2247条查询结果,搜索用时 31 毫秒
1.
Ewa Maria Kratz Katarzyna Sokiewicz Adriana Kubis-Kubiak Agnieszka Piwowar 《International journal of molecular sciences》2021,22(2)
Sirtuins (SIRTs), enzymes from the family of NAD+-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results. 相似文献
2.
Agnieszka Rybarczyk-Kasiuchnicz Rodryg Ramlau Katarzyna Stencel 《International journal of molecular sciences》2021,22(2)
Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases. 相似文献
3.
Vancha Harish Effi Haque Magdalena
miech Hiroaki Taniguchi Sarah Jamieson Devesh Tewari Anupam Bishayee 《International journal of molecular sciences》2021,22(9)
Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure–activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers. 相似文献
4.
Ewa Olewnik-Kruszkowska Magdalena Gierszewska Sylwia Grabska-Zieliska Joanna Skopiska-Winiewska Ewelina Jakubowska 《International journal of molecular sciences》2021,22(7)
Hydrogels based on chitosan are very versatile materials which can be used for tissue engineering as well as in controlled drug delivery systems. One of the methods for obtaining a chitosan-based hydrogel is crosslinking by applying different components. The objective of the present study was to obtain a series of new crosslinked chitosan-based films by means of solvent casting method. Squaric acid—3,4-dihydroxy-3-cyclobutene-1,2-dione—was used as a safe crosslinking agent. The effect of the squaric acid on the structural, mechanical, thermal, and swelling properties of the formed films was determined. It was established that the addition of the squaric acid significantly improved Young’s modulus, tensile strength, and thermal stability of the obtained materials. Moreover, it should be stressed that the samples consisting of chitosan and squaric acid were characterized by a higher swelling than pure chitosan. The detailed characterization proved that squaric acid could be used as a new effective crosslinking agent. 相似文献
5.
Ryszard Żywica Monika Modzelewska-Kapituła Katarzyna Tkacz 《International Journal of Food Properties》2018,21(1):1386-1394
The aim of the present study was to determine mathematical relationships between pH changes in beef 24 h post-slaughter and changes in the intensity of electrical current flowing through bull and heifer carcasses during high-voltage electrical stimulation. The electrical stimulation was applied 40 min postmortem for 120 s. The pH values of m. longissimus thoracis et lumborum were analyzed in the function of electrical current intensity changes and its change during electrical stimulation. Mathematical linear correlations of the y = ax ± b type were demonstrated between pH values at 2, 6, and 24 h postmortem and the initial (Ii) and ultimate (Iu) electrical current intensity values, the difference between them and the initial pH values determined before electrical stimulation. High multiple correlation coefficients (R2 = 0.416, α ≤ 0.001) between Iu and pH values 24 h post-slaughter enabled concluding that there is a possibility to predict a pH value of stimulated carcass with high accuracy, and thus also beef quality, based merely on the ultimate electrical current intensity values. 相似文献
6.
7.
8.
Teresa Glomb Benita Wiatrak Katarzyna Gbczak Tomasz Gbarowski Dorota Bodetko aneta Czynikowska Piotr
witek 《International journal of molecular sciences》2020,21(23)
Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases. 相似文献
9.
Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
Beata Filip-Psurska Mateusz Psurski Artur Anisiewicz Patrycja Libako Ewa Zbrojewicz Magdalena Maciejewska Micha Chodyski Andrzej Kutner Joanna Wietrzyk 《International journal of molecular sciences》2021,22(5)
1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR. 相似文献