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951.
952.
用电化学循环伏安法和微分脉冲伏安法研究了1,10-邻菲咯啉铜配合物[(phen)2Cu^2+]与小牛胸腺DNA(CTDNA)的相互作用。结果发现,在pH=7.4的三羟甲基胺基甲烷-盐酸缓冲溶液(Tris—HCl)中,(phen)2Cu^2+配合物的铜离子在循环伏安图上呈现明显的准可逆氧化-还原波。当加入一定量的小牛胸腺DNA时,配合物(phen),Cu^2+的氧化和还原峰电流均有所下降。通过比较(phen)2Cu^2+配合物中加入单链DNA和双链DNA后的氧化和还原峰电流下降的程度,前者比后者F降的程度小,可以得出(phen)2Cu^2+配合物与小牛胸腺双链DNA的作用方式存在着插入式的沟槽结合模式。这个结论在本实验中由盐效应进一步得到证实。由此可知,(phen)2Cu^2+配合物与小牛胸腺DNA形成了一种插入式的电惰性结合物,从而导致氧化还原峰电流下降。 相似文献
953.
Na Young Kim Chakrabhavi Dhananjaya Mohan Arunachalam Chinnathambi Sulaiman Ali Alharbi Gautam Sethi Kanchugarakoppal S. Rangappa Kwang Seok Ahn 《Molecules (Basel, Switzerland)》2022,27(12)
EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3βS9 with a parallel increase in β-TrCP and phosphorylation of GSK-3βY216. Lithium chloride treatment increased the phosphorylation of GSK-3βS9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells. 相似文献
954.
Bin-Long Sun Ying-Ying Wang Sen Yang Min-Ting Tu Ying-Ying Shao Yi Hua Yi Zhou Cheng-Xia Tan 《Molecules (Basel, Switzerland)》2022,27(12)
To develop new compounds with high activity, broad spectrum and low-toxicity, 17 benzamides substituted with quinoline-linked 1,2,4-oxadiazole were designed using the splicing principle of active substructures and were synthesized. The biological activities were evaluated against 10 fungi, indicating that some of the synthetic compounds showed excellent fungicidal activities. For example, at 50 mg/L, the inhibitory activity of 13p (3-Cl-4-Cl substituted, 86.1%) against Sclerotinia sclerotiorum was superior to that of quinoxyfen (77.8%), and the inhibitory activity of 13f (3-CF3 substituted, 77.8%) was comparable to that of quinoxyfen. The fungicidal activities of 13f and 13p to Sclerotinia sclerotiorum were better than that of quinoxyfen (14.19 mg/L), with EC50 of 6.67 mg/L and 5.17 mg/L, respectively. Furthermore, the acute toxicity of 13p was 19.42 mg/L, classifying it as a low-toxic compound. 相似文献
955.
Steven Elder John Graham Roberson James Warren Robert Lawson Daniel Young Sean Stokes Matthew K. Ross 《Molecules (Basel, Switzerland)》2022,27(12)
In this study, kartogenin was incorporated into an electrospun blend of polycaprolactone and poly(lactic-co-glycolic acid) (1:1) to determine the feasibility of this system for sustained drug delivery. Kartogenin is a small-molecule drug that could enhance the outcome of microfracture, a cartilage restoration procedure, by selectively stimulating chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells. Experimental results showed that kartogenin did not affect the electrospinnability of the polymer blend, and it had negligible effects on fiber morphology and scaffold mechanical properties. The loading efficiency of kartogenin into electrospun membranes was nearly 100%, and no evidence of chemical reaction between kartogenin and the polymers was detected by Fourier transform infrared spectroscopy. Analysis of the released drug using high-performance liquid chromatography–photodiode array detection indicated an abundance of kartogenin and only a small amount of its major hydrolysis product. Kartogenin displayed a typical biphasic release profile, with approximately 30% being released within 24 h followed by a much slower, constant rate of release up to 28 days. Although additional development is needed to tune the release kinetics and address issues common to electrospun scaffolds (e.g., high fiber density), the results of this study demonstrated that a scaffold electrospun from biodegradable synthetic polymers is a suitable kartogenin delivery vehicle. 相似文献
956.
Yi Wang Xiangli Zhang Wenya Zhuang Yanlei Yu Xuanrong Sun Hong Wang Fengzhi Li Qingyong Li 《Molecules (Basel, Switzerland)》2022,27(12)
Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118. The transport and uptake of FL118, FL77-28, and FL77-29 were investigated in Caco-2 cells for the preliminary prediction of intestinal absorption. The apparent permeability coefficient from apical to basolateral (Papp AP-BL) values of FL77-28 and FL77-29 were (2.32 ± 0.04) × 10−6 cm/s and (2.48 ± 0.18) × 10−6 cm/s, respectively, suggesting that the compounds had moderate absorption. Since the transport property of FL77-28 was passive diffusion and the efflux ratio (ER) was less than 2, two chemical inhibitors were added to further confirm the involvement of efflux proteins. The results showed that FL77-28 was not a substrate of P-gp or BCRP, but FL77-29 was mediated by P-gp. In conclusion, FL77-28 might be a promising candidate to overcome drug resistance induced by multiple efflux proteins. 相似文献
957.
Alena L. Stalinskaya Nadezhda V. Martynenko Zarina T. Shulgau Alexandr V. Shustov Viktoriya V. Keyer Ivan V. Kulakov 《Molecules (Basel, Switzerland)》2022,27(12)
The COVID-19 pandemic is ongoing as of mid-2022 and requires the development of new therapeutic drugs, because the existing clinically approved drugs are limited. In this work, seven derivatives of epoxybenzooxocinopyridine were synthesized and tested for the ability to inhibit the replication of the SARS-CoV-2 virus in cell cultures. Among the described compounds, six were not able to suppress the SARS-CoV-2 virus’ replication. One compound, which is a derivative of epoxybenzooxocinopyridine with an attached side group of 3,4-dihydroquinoxalin-2-one, demonstrated antiviral activity comparable to that of one pharmaceutical drug. The described compound is a prospective lead substance, because the half-maximal effective concentration is 2.23 μg/μL, which is within a pharmacologically achievable range. 相似文献
958.
Shengying Lin Xiaoyang Wang Roy Wai-Lun Tang Hung Chun Lee Ho Hin Chan Sheyne S. A. Choi Tina Ting-Xia Dong Ka Wing Leung Sarah E. Webb Andrew L. Miller Karl Wah-Keung Tsim 《Molecules (Basel, Switzerland)》2022,27(12)
COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC50 values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19. 相似文献
959.
给出了求解多自由度动力学系统响应的M atlab程序,这些程序基于振型叠加法可用于求解由质量矩阵M和刚度矩阵K以及常见阻尼矩阵描述的线性离散系统的时域和频域解.对于无阻尼系统,用户可以选择数值解或符号解析解(以时间或频率表示),并利用复模态叠加法计算了阻尼系统的数值解.总结了模态叠加方法下动力学响应的求解,并在简短的M... 相似文献
960.
Yuri Hirayama Naohiko Anzai Hiroyuki Kinouchi Schuichi Koizumi 《Molecules (Basel, Switzerland)》2022,27(12)
A sub-lethal ischemic episode (preconditioning [PC]) protects neurons against a subsequent lethal ischemic injury. This phenomenon is known as ischemic tolerance. PC itself does not cause brain damage, but affects glial responses, especially astrocytes, and transforms them into an ischemia-resistant phenotype. P2X7 receptors (P2X7Rs) in astrocytes play essential roles in PC. Although P2X7Rs trigger inflammatory and toxic responses, PC-induced P2X7Rs in astrocytes function as a switch to protect the brain against ischemia. In this review, we focus on P2X7Rs and summarize recent developments on how astrocytes control P2X7Rs and what molecular mechanisms they use to induce ischemic tolerance. 相似文献