全文获取类型
收费全文 | 2729篇 |
免费 | 201篇 |
国内免费 | 124篇 |
专业分类
3054篇 |
出版年
2023年 | 23篇 |
2022年 | 57篇 |
2021年 | 105篇 |
2020年 | 72篇 |
2019年 | 90篇 |
2018年 | 106篇 |
2017年 | 73篇 |
2016年 | 88篇 |
2015年 | 160篇 |
2014年 | 159篇 |
2013年 | 218篇 |
2012年 | 225篇 |
2011年 | 180篇 |
2010年 | 128篇 |
2009年 | 103篇 |
2008年 | 95篇 |
2007年 | 112篇 |
2006年 | 105篇 |
2005年 | 107篇 |
2004年 | 105篇 |
2003年 | 80篇 |
2002年 | 55篇 |
2001年 | 64篇 |
2000年 | 55篇 |
1999年 | 55篇 |
1998年 | 28篇 |
1997年 | 26篇 |
1996年 | 23篇 |
1995年 | 28篇 |
1994年 | 27篇 |
1993年 | 19篇 |
1992年 | 39篇 |
1991年 | 30篇 |
1990年 | 18篇 |
1989年 | 22篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 13篇 |
1985年 | 15篇 |
1984年 | 17篇 |
1983年 | 17篇 |
1982年 | 14篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1971年 | 8篇 |
排序方式: 共有3054条查询结果,搜索用时 0 毫秒
31.
Jingxiang Pang Meina Yang Jialei Fu Xiaolei Zhao Eduard van Wijk Mei Wang Yanli Liu Xiaoyan Zhou Hua Fan Jinxiang Han 《Luminescence》2016,31(2):491-498
Traditional Chinese material medica are an important component of the Chinese pharmacopeia. According to the traditional Chinese medicinal concept, Chinese herbal medicines are classified into different categories based on their therapeutic effects, however, the bioactive principles cannot be solely explained by chemical analysis. The aim of this study is to classify different Chinese herbs based on their therapeutic effects by using delayed luminescence (DL). The DL of 56 Chinese herbs was measured using an ultra‐sensitive luminescence detection system. The different DL parameters were used to classify Chinese herbs according to a hierarchical cluster analysis. The samples were divided into two groups based on their DL kinetic parameters. Interestingly, the DL classification results were quite consistent with classification according to the Chinese medicinal concepts of ‘cold’ and ‘heat’ properties. In this paper, we show for the first time that by using DL technology, it is possible to classify Chinese herbs according to the Chinese medicinal concept and it may even be possible to predict their therapeutic properties. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
32.
Optimization of a serotype-selective, small-molecule inhibitor of botulinum neurotoxin serotype A (BoNTA) endopeptidase is a formidable challenge because the enzyme-substrate interface is unusually large and the endopeptidase itself is a large, zinc-binding protein with a complex fold that is difficult to simulate computationally. We conducted multiple molecular dynamics simulations of the endopeptidase in complex with a previously described inhibitor (K(i) (app) of 7+/-2.4 microM) using the cationic dummy atom approach. Based on our computational results, we hypothesized that introducing a hydroxyl group to the inhibitor could improve its potency. Synthesis and testing of the hydroxyl-containing analog as a BoNTA endopeptidase inhibitor showed a twofold improvement in inhibitory potency (K(i) (app) of 3.8+/-0.8 microM) with a relatively small increase in molecular weight (16 Da). The results offer an improved template for further optimization of BoNTA endopeptidase inhibitors and demonstrate the effectiveness of the cationic dummy atom approach in the design and optimization of zinc protease inhibitors. 相似文献
33.
34.
C.W. Tsang C.L. Chan P. Li S.F. Pang 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,682(2):185
A sensitive method for the measurement of endogenous 5-methoxytryptamine in brain tissue has been developed using capillary column gas chromatography-electron-capture negative-ion chemical ionization mass spectrometry. 5-Methoxytryptamine was first converted to N-[2H3]acetyl-5-methoxytryptamine by reaction with hexa-deuterated acetic anhydride, followed by reaction with pentafluoropropionic anhydride to yield the highly electron-capturing 3,3′-spirocyclic pentafluoropropionyl indolenine derivative. Quantitative analysis was carried out by selected-ion monitoring of the [M-HF] and [M-HF-DF] ion intensity of the 3,3′-spirocyclic pentafluoropropionyl indolenine derivative, using 5-methoxy-[α,α,β,β-2H4]tryptamine as the internal standard. The presence of 5-methoxytryptamine in the brain tissue was demonstrated. In the absence of a monoamine oxidase inhibitor, the mean±S.D. levels of 5-methoxytryptamine in the rat and quail whole brain were found to be 30±6 and 347±52 pg/g, respectively. The possible physiological functions of 5-methoxytryptamine as a neuromodulator and/or neurotransmitter have to be considered. 相似文献
35.
Yuanzhou Zhang Shunshun Liang Bowen Xiao Jingying Hu Yechun Pang Yuling Liu Juan Yang Junpin Ao Lin Wei Xiaoying Luo 《Cell death & disease》2022,13(3)
The rapid onset of resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) limits its clinical utility in colorectal cancer (CRC) patients, and pan-erb-b2 receptor tyrosine kinase (ErbB) treatment strategy may be the alternative solution. The aim of this study was to develop a possible microRNA multi-ErbB treatment strategy to overcome EGFR-TKI resistance. We detect the receptor tyrosine kinase activity in gefitinib-resistant colorectal cancer cells, ErbB3/EGFR is significantly activated and provides a potential multi-ErbB treatment target. MiR-323a-3p, a tumor suppressor, could target both ErbB3 and EGFR directly. Apoptosis is the miR-323a-3p inducing main biological process by functional enrichment analysis, and The EGFR and ErbB signaling are the miR-323a-3p inducing main pathway by KEGG analysis. MiR-323a-3p promotes CRC cells apoptosis by targeting ErbB3-phosphoinositide 3‐kinases (PI3K)/PKB protein kinase (Akt)/glycogen synthase kinase 3 beta (GSK3β)/EGFR-extracellular regulated MAP kinase (Erk1/2) signaling directly. And miR-323a-3p, as a multi-ErbBs inhibitor, increase gefitinib sensitivity of the primary cell culture from combination miR-323a-3p and gefitinib treated subcutaneous tumors. MiR-323a-3p reverses ErbB3/EGFR signaling activation in gefitinib-resistant CRC cell lines and blocks acquired gefitinib resistance.Subject terms: Colorectal cancer, Cancer therapeutic resistance 相似文献
36.
稀疏效应下周期系数捕食-被捕食系统的全局渐近稳定性 总被引:2,自引:0,他引:2
研究一类稀疏效应下周期系数捕食-被捕食系统,得到了该系统存在唯一全局渐近稳定的正周期解的充分条件. 相似文献
37.
Serum amyloid A 2.1 (SAA2.1) suppresses ACAT and stimulates cholesteryl ester hydrolase (CEH) activities in cholesterol-laden macrophages, and in the presence of a cholesterol transporter and an extracellular acceptor, there is a marked increase in the rate of cholesterol export in culture and in vivo. The stimulation of CEH activity by SAA2.1 is not affected by chloroquine, suggesting that it operates on neutral CEH rather than the lysosomal form. With liposomes containing individual peptides of SAA2.1, residues 1-20 inhibit ACAT activity, residues 74-103 stimulate CEH activity, and each of residues 1-20 and 74-103 promotes macrophage cholesterol efflux to HDL in culture media. In combination, these peptides exhibit a profound effect, so that 55-70% of cholesterol is exported to media HDL in 24 h. The effect is also demonstrable in vivo. [3H]cholesterol-laden macrophages injected intravenously into mice were allowed to establish themselves for 24 h. Thereafter, the mice received a single intravenous injection of liposomes containing intact SAA1.1, SAA2.1, peptides composed of SAA2.1 residues 1-20, 21-50, 51-80, 74-103, or SAA1.1 residues 1-20. Only liposomes containing intact SAA2.1 or its residues 1-20 or 74-103 promoted the efflux of cholesterol in vivo. A single injection of each of the active peptides is effective in promoting cholesterol efflux in vivo for at least 4 days. 相似文献
38.
Xiaohui Pang Chang Liu Linchun Shi Rui Liu Dong Liang Huan Li Stacey S. Cherny Shilin Chen 《PloS one》2012,7(11)
Background
The trnH–psbA intergenic spacer region has been used in many DNA barcoding studies. However, a comprehensive evaluation with rigorous sequence preprocessing and statistical testing on the utility of trnH–psbA and its combinations as DNA barcodes is lacking.Methodology/Principal Findings
Sequences were searched from GenBank for a meta-analysis on the usefulness of trnH–psbA and its combinations as DNA barcodes. After preprocessing, we constructed full and matching data sets that contained 17 983 trnH–psbA sequences and 2190 sets of trnH–psbA, matK, rbcL, and ITS2 sequences from the same sample, repectively. These datasets were used to analyze the ability of trnH–psbA and its combinations to discriminate species by the BLAST and BLAST+P methods. The Fisher''s exact test was used to evaluate the significance of performance differences. For the full data set, the identification success rates of trnH–psbA exceeded 70% in 18 families and 12 genera, respectively. For the matching data set, the identification rates of trnH–psbA were significantly higher than those of the other loci in two families and four genera. Similarly, the identification rates of trnH–psbA+ITS2 were significantly higher than those of matK+rbcL in 18 families and 21 genera.Conclusion/Significane
This study provides valuable information on the higher utility of trnH–psbA and its combinations. We found that trnH–psbA+ITS2 combination performs better or equally well compared with other combinations in most taxonomic groups investigated. This information will guide the optimal usage of trnH–psbA and its combinations for species identification. 相似文献39.
40.
Tingting Wang Guoxiang Cai Yunping Qiu Na Fei Menghui Zhang Xiaoyan Pang Wei Jia Sanjun Cai Liping Zhao 《The ISME journal》2012,6(2):320-329
Despite a long-suspected role in the development of human colorectal cancer (CRC), the composition of gut microbiota in CRC patients has not been adequately described. In this study, fecal bacterial diversity in CRC patients (n=46) and healthy volunteers (n=56) were profiled by 454 pyrosequencing of the V3 region of the 16S ribosomal RNA gene. Both principal component analysis and UniFrac analysis showed structural segregation between the two populations. Forty-eight operational taxonomic units (OTUs) were identified by redundancy analysis as key variables significantly associated with the structural difference. One OTU closely related to Bacteroides fragilis was enriched in the gut microbiota of CRC patients, whereas three OTUs related to Bacteroides vulgatus and Bacteroides uniformis were enriched in that of healthy volunteers. A total of 11 OTUs belonging to the genera Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus and Peptostreptococcus were significantly more abundant in the gut microbiota of CRC patients, and 5 OTUs belonging to the genus Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae were less abundant. Real-time quantitative PCR further validated the significant reduction of butyrate-producing bacteria in the gut microbiota of CRC patients by measuring the copy numbers of butyryl-coenzyme A CoA transferase genes (Mann–Whitney test, P<0.01). Reduction of butyrate producers and increase of opportunistic pathogens may constitute a major structural imbalance of gut microbiota in CRC patients. 相似文献