全文获取类型
收费全文 | 2246篇 |
免费 | 95篇 |
国内免费 | 287篇 |
出版年
2023年 | 106篇 |
2022年 | 138篇 |
2021年 | 131篇 |
2020年 | 211篇 |
2019年 | 260篇 |
2018年 | 241篇 |
2017年 | 196篇 |
2016年 | 163篇 |
2015年 | 66篇 |
2014年 | 145篇 |
2013年 | 312篇 |
2012年 | 108篇 |
2011年 | 53篇 |
2010年 | 45篇 |
2009年 | 37篇 |
2008年 | 34篇 |
2007年 | 32篇 |
2006年 | 27篇 |
2005年 | 34篇 |
2004年 | 20篇 |
2003年 | 17篇 |
2002年 | 28篇 |
2001年 | 8篇 |
2000年 | 12篇 |
1999年 | 11篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1993年 | 4篇 |
1991年 | 5篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 13篇 |
1984年 | 19篇 |
1983年 | 11篇 |
1982年 | 16篇 |
1981年 | 11篇 |
1980年 | 16篇 |
1979年 | 12篇 |
1978年 | 12篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 4篇 |
1974年 | 9篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有2628条查询结果,搜索用时 31 毫秒
1.
Ehsan Ullah Mughal Amina Sadiq Shahzad Murtaza Hummera Rafique Muhammad Naveed Zafar Tauqeer Riaz Bilal Ahmad Khan Abdul Hameed Khalid Mohammed Khan 《Bioorganic & medicinal chemistry》2017,25(1):100-106
The present study describes efficient and facile syntheses of varyingly substituted 3-thioaurones from the corresponding 3-oxoaurones using Lawesson’s reagent and phosphorous pentasulfide. In comparison, the latter methodology was proved more convenient, giving higher yields and required short and simple methodology. The structures of synthetic compounds were unambiguously elucidated by IR, MS and NMR spectroscopy. All synthetic compounds were screened for their inhibitory potential against in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Molecular docking studies were also performed in order to examine their binding interactions with AChE and BChE human proteins. Both studies revealed that some of these compounds were found to be good inhibitors against AChE and BChE. 相似文献
2.
Subhadip Hajra Abhishek Basu Somnath Singha Roy Arup Ranjan Patra Sudin Bhattacharya 《Free radical research》2017,51(9-10):812-827
The most crucial complication related to doxorubicin (DOX) therapy is nonspecific cytotoxic effect on healthy normal cells. The clinical use of this broad-spectrum chemotherapeutic agent is restricted due to development of severe form of cardiotoxicity, myelosuppression, and genotoxicity which interfere with therapeutic schedule, compromise treatment outcome and may lead to secondary malignancy. 3,3′-diindolylmethane (DIM) is a naturally occurring plant alkaloid formed by the hydrolysis of indolylmethyl glucosinolate (glucobrassicin). Therefore, the present study was undertaken to investigate the protective role of DIM against DOX-induced toxicity in mice. DOX was administered (5?mg/kg b.w., i.p.) and DIM was administered (25?mg/kg b.w., p.o.) in concomitant and 15 days pretreatment schedule. Results showed that DIM significantly attenuated DOX-induced oxidative stress in the cardiac tissues by reducing the levels of free radicals and lipid peroxidation, and by enhancing the level of glutathione (reduced) and the activity of antioxidant enzymes. The chemoprotective potential of DIM was confirmed by histopathological evaluation of heart and bone marrow niche. Moreover, DIM considerably mitigated DOX-induced clastogenicity, DNA damage, apoptosis, and myeloid hyperplasia in bone marrow niche. In addition, oral administration of DIM significantly (p?.05) stimulated the Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, HO-1, NQO1, and glutathione-S-transferase (GST). In connection with that, DIM significantly attenuated DOX-induced apoptosis by upregulation of Bcl-2 expression and downregulation of Bax and caspase-3 expression. Thus, this study suggests that DIM has promising chemoprotective efficacy against DOX-induced toxicity and indicates its future use as an adjuvant in chemotherapy. 相似文献
3.
The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to attenuate disease progression. 相似文献
4.
《Bioorganic & medicinal chemistry letters》2014,24(18):4523-4528
Osmolytes have been proposed as treatments for neurodegenerative proteinopathies including Alzheimer’s disease. However, for osmolytes to reach the clinic their efficacy must be improved. In this work, copper(I)-catalyzed azide–alkyne cycloaddition chemistry was used to synthesize glycoclusters bearing six copies of trehalose, lactose, galactose or glucose, with the aim of improving the potency of these osmolytes via multivalency. A trehalose glycocluster was found to be superior to monomeric trehalose in its ability to retard the formation of amyloid-beta peptide 40 (Aβ40) fibrils and protect neurons from Aβ40-induced cell death. 相似文献
5.
《Bioorganic & medicinal chemistry letters》2019,29(15):1957-1961
In our efforts to further investigate the impact of the spacer and membrane anchor to the neuroprotective activities, a series of bivalent compounds that contain cholesterol and extended spacers were designed, synthesized and biologically characterized. Our results support previous studies that incorporation of a piperazine ring into the spacer significantly improved the protective potency of bivalent compounds in MC65 cell model. Spacer length beyond 21 atoms does not add further benefits with 21MO being the most potent one with an EC50 of 81.86 ± 11.91 nM. Our results also demonstrated that bivalent compound 21MO suppressed the production of mitochondria reactive oxygen species. Furthermore, our results confirmed that both of the spacer and membrane anchor moiety are essential to metal binding. Collectively, the results provide further evidence and information to guide optimization of such bivalent compounds as potential neuroprotectants for Alzheimer’s disease. 相似文献
6.
《Bioorganic & medicinal chemistry letters》2014,24(24):5805-5813
The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile. 相似文献
7.
In order to improve the conservation status of the Eld’s Deer (Cervus eldii), a critically endangered species in China, a population in a nature reserve on Hainan Island was studied. Abundances and behaviours in two different habitat types, natural and manipulated, were recorded. We found that different habitats were preferred according to season. Both sexes were more abundant in the manipulated habitat from January to May, with males being more abundant in the natural habitat from September to October. However, females, were significantly more abundant from April and May in the manipulated habitat. The deer preferred the more open manipulated habitat for feeding, consistent with greater food availability. This study provides useful evidence for managers to create seasonally suitable habitat for the conservation of this species on Hainan Island. Similar methods could also be applied to other deer species in China, most of which are facing critical survival challenges. 相似文献
8.
A series of thirty (30) thiazole analogs were prepared, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59 ± 0.01 and 389.25 ± 1.75 μM when compared with the standard eserine (IC50, 0.85 ± 0.0001 μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59 ± 0.01, 1.77 ± 0.01, 6.21 ± 0.01, 7.56 ± 0.01, 8.46 ± 0.01, 14.81 ± 0.32 and 16.54 ± 0.21 μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3 ± 0.50, 35.3 ± 0.64, 36.6 ± 0.70, 44.81 ± 0.81, 46.36 ± 0.84, 48.2 ± 0.06 and 48.72 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking. 相似文献
9.
A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer’s disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068 μM and 0.0089 μM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114 µM for hAChE; 0.101 µM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500 mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold. 相似文献
10.
在有人为干扰的森林景观中开展鹿科动物适宜生境分布研究,对于解决大尺度生境保护与小面积森林经营的矛盾问题有着重要的参考意义,也符合我国林区的现实需求.2013—2015年冬季进行的多次野外调查收集196处鹿科动物出现点信息,将这些点作为分布点数据,选取地形、景观类型、植被特征和人类干扰4类17种因子作为环境变量,利用最大熵模型方法,分析4种林下经营面积情景下小兴安岭铁力林业局马鹿和狍的潜在适宜生境分布特征及其对环境因子的响应.结果表明:模型预测精度达到优秀水平,稳定性好,鹿科动物的适宜生境主要集中在东部区域;不同情景下,两种鹿科动物的主要环境影响因子相似,均为距农田距离、距居民点距离、距河流距离、距营林区距离和海拔因子,其中,距营林区距离因子的贡献率稳定在4%~6%;两种鹿科动物躲避人类经营活动干扰的距离(1200~1300 m)较为接近.在无林下经营情景中,鹿科动物的适宜生境分布较广、面积较大;随着经营面积的增大,适宜生境面积减少;当经营面积扩大到现实情况的2~3倍时,鹿科动物栖息地面积缩减较为严重. 相似文献