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131.
Anita Romanowska Katarzyna Wgrzyn Katarzyna Bury Emilia Sikorska Aleksandra Gnatek Agnieszka Piwkowska Igor Konieczny Adam Lesner Magdalena Wysocka 《International journal of molecular sciences》2021,22(5)
The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)n-O2Oc-NH2, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]8-O2Oc-NH2 and typical for large proteins. 相似文献
132.
利用多功能改进型索氏提取器为提取工具,以人参须根粉为原料,盐酸为催化剂,分子筛辅助下高效制备了稀有人参皂苷Rg5,并通过单因素实验优化了工艺条件。实验结果表明:当以30 mL的甲醇为溶剂、加入0.3 g 4 A分子筛、于65 ℃提取4 h时,人参总皂苷的提取率达到10.2%,稀有人参皂苷Rg5的得率达到3.20%,与传统索氏提取器相比可以显著提高人参皂苷Rg5的制备效率。分子筛辅助下利用多功能改进型索氏提取器从人参须根粉提取制备稀有人参皂苷Rg5,不仅得率较高,而且操作简单快捷,是一种快速制备人参皂苷Rg5的工艺方法。 相似文献
133.
目的改良HPLC(AKTA层析)系统,采用HPLC-MALLS系统检测b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)精制多糖的分子大小分布及重均分子质量(MW),并进行方法的验证。方法采用HPLC(AKTA层析)系统连接示差分析仪检测9批Hib精制多糖供试品的分配系数(KD)及KD值为0.5的回收率(RX)。采用HPLC连接18角度静态光散射分析系统MALLS(HPLC-MALLS)检测供试品的MW、KD及RX,并对两种系统的测试结果进行相关性分析;验证HPLC-MALLS方法的重复性、准确性及定量限。结果 9批供试品经AKTA层析系统检测,KD为0.29~0.37,RX为78%~90%;经HPLC-MALLS系统检测,KD为0.31~0.38,RX为84%~93%,MW为(1.418~2.281)×105g/moL,两种系统检测同批供试品的KD值回归方程为Y=0.903 X+0.051,r为0.978,表明检测结果具有显著相关性,两种方法等效。9批供试品经HPLC-MALLS/RI系统重复检测6次,MW、KD及RX的RSD均小于3.8%,多糖回收率及其RSD分别为80%~87%和0.05%~3.46%;定量限为1 mg/mL。结论 HPLC-MALLS系统能与HPLC系统基本对接,在准确检测Hib精制多糖MW的同时还可检测KD及RX,且方法的准确性及重复性良好,可作为检测Hib精制多糖分子大小的改良方法。 相似文献
134.
AKT, is a serine/threonine protein kinase comprising three isoforms—namely: AKT1, AKT2 and AKT3, whose inhibitors have been recognized as promising therapeutic targets for various human disorders, especially cancer. In this work, we report a systematic evaluation of multi-target Quantitative Structure-Activity Relationship (mt-QSAR) models to probe AKT’ inhibitory activity, based on different feature selection algorithms and machine learning tools. The best predictive linear and non-linear mt-QSAR models were found by the genetic algorithm-based linear discriminant analysis (GA-LDA) and gradient boosting (Xgboost) techniques, respectively, using a dataset containing 5523 inhibitors of the AKT isoforms assayed under various experimental conditions. The linear model highlighted the key structural attributes responsible for higher inhibitory activity whereas the non-linear model displayed an overall accuracy higher than 90%. Both these predictive models, generated through internal and external validation methods, were then used for screening the Asinex kinase inhibitor library to identify the most potential virtual hits as pan-AKT inhibitors. The virtual hits identified were then filtered by stepwise analyses based on reverse pharmacophore-mapping based prediction. Finally, results of molecular dynamics simulations were used to estimate the theoretical binding affinity of the selected virtual hits towards the three isoforms of enzyme AKT. Our computational findings thus provide important guidelines to facilitate the discovery of novel AKT inhibitors. 相似文献
135.
Andrea Kunova Luca Palazzolo Fabio Forlani Giorgia Catinella Loana Musso Paolo Cortesi Ivano Eberini Andrea Pinto Sabrina Dallavalle 《International journal of molecular sciences》2021,22(7)
The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen. 相似文献
136.
Zhongjie Yu Yashuo Wang Lili Liu Xianjuan Zhang Shasha Jiang Bin Wang 《International journal of molecular sciences》2021,22(8)
Human cytomegalovirus (HCMV) belongs to the β-herpesvirus family, which is transmitted in almost every part of the world and is carried by more than 90% of the general population. Increasing evidence indicates that HCMV infection triggers numerous diseases by disrupting the normal physiological activity of host cells, particularly apoptosis. Apoptosis disorder plays a key role in the initiation and development of multiple diseases. However, the relationship and molecular mechanism of HCMV-related diseases and apoptosis have not yet been systematically summarized. This review aims to summarize the role of apoptosis in HCMV-related diseases and provide an insight into the molecular mechanism of apoptosis induced by HCMV infection. We summarize the literature on HCMV-related diseases and suggest novel strategies for HCMV treatment by regulating apoptosis. 相似文献
137.
Alfredo Jurez-Saldivar Elizabeth Barbosa-Cabrera Edgar E. Lara-Ramírez Alma D. Paz-Gonzlez Ana V. Martínez-Vzquez Virgilio Bocanegra-García Isidro Palos Nuria E. Campillo Gildardo Rivera 《International journal of molecular sciences》2021,22(11)
Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL). 相似文献
138.
Bilal Ahmad Maria Batool Moon-Suk Kim Sangdun Choi 《International journal of molecular sciences》2021,22(11)
Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics. 相似文献
139.
Natasha M. van Poppelen Jolique A. van Ipenburg Quincy van den Bosch Jolanda Vaarwater Tom Brands Bert Eussen Frank Magielsen Hendrikus J. Dubbink Dion Paridaens Erwin Brosens Nicole Naus Annelies de Klein Emine Kili Robert M. Verdijk 《International journal of molecular sciences》2021,22(11)
The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM. 相似文献
140.