全文获取类型
收费全文 | 3216篇 |
免费 | 231篇 |
国内免费 | 268篇 |
出版年
2024年 | 4篇 |
2023年 | 27篇 |
2022年 | 40篇 |
2021年 | 136篇 |
2020年 | 118篇 |
2019年 | 108篇 |
2018年 | 102篇 |
2017年 | 89篇 |
2016年 | 140篇 |
2015年 | 205篇 |
2014年 | 233篇 |
2013年 | 285篇 |
2012年 | 251篇 |
2011年 | 279篇 |
2010年 | 168篇 |
2009年 | 148篇 |
2008年 | 194篇 |
2007年 | 189篇 |
2006年 | 186篇 |
2005年 | 144篇 |
2004年 | 118篇 |
2003年 | 80篇 |
2002年 | 79篇 |
2001年 | 27篇 |
2000年 | 30篇 |
1999年 | 46篇 |
1998年 | 37篇 |
1997年 | 46篇 |
1996年 | 48篇 |
1995年 | 34篇 |
1994年 | 21篇 |
1993年 | 21篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有3715条查询结果,搜索用时 16 毫秒
81.
Activated persulfate oxidation technologies based on sulfate radicals were first evaluated for defluorination of aqueous perfluorooctanesulfonate (PFOS). The influences of catalytic method, time, pH and K2S2O8 amounts on PFOS defluorination were investigated. The intermediate products during PFOS defluorination were detected by using LC/MS/MS. The results showed that the S2O8
2− had weak effect on the defluorination of PFOS, while the PFOS was oxidatively defluorinated by sulfate radicals in water. The defluorination efficiency of PFOS under various treatment was followed the order: HT (hydrothermal)/K2S2O8 > UV (ultraviolet)/K2S2O8 > Fe2+/K2S2O8 > US (ultrasound)/K2S2O8. Low pH was favorable for the PFOS defluorination with sulfate radicals. Increase in the amount of S2O8
2− had positive effect on PFOS defluorination. However, further increase in amounts of S2O8
2− caused insignificant improvement in PFOS defluorination due to elimination of sulfate radicals under high concentration of S2O8
2−. CF3(CF2)nCOOH (n = 0–6) were detected as intermediates during PFOS defluorination. Sulfate radicals oxidation and hydrolysis were the main mechanisms involved in defluorination process of PFOS. 相似文献
82.
Yuhong Zhang Xiaolu Xu Xiaojin Zhou Rumei Chen Peilong Yang Qingchang Meng Kun Meng Huiying Luo Jianhua Yuan Bin Yao Wei Zhang 《PloS one》2013,8(12)
Background
Incorporation of exogenous glucanase into animal feed is common practice to remove glucan, one of the anti-nutritional factors, for efficient nutrition absorption. The acidic endo-β-1,3-1,4-glucanase (Bgl7A) from Bispora sp. MEY-1 has excellent properties and represents a potential enzyme supplement to animal feed.Methodology/Principal Findings
Here we successfully developed a transgenic maize producing a high level of Bgl7AM (codon modified Bgl7A) by constructing a recombinant vector driven by the embryo-specific promoter ZM-leg1A. Southern and Western blot analysis indicated the stable integration and specific expression of the transgene in maize seeds over four generations. The β-glucanase activity of the transgenic maize seeds reached up to 779,800 U/kg, about 236-fold higher than that of non-transgenic maize. The β-glucanase derived from the transgenic maize seeds had an optimal pH of 4.0 and was stable at pH 1.0–8.0, which is in agreement with the normal environment of digestive tract.Conclusion/Significance
Our study offers a transgenic maize line that could be directly used in animal feed without any glucanase production, purification and supplementation, consequently simplifying the feed enzyme processing procedure. 相似文献83.
84.
Zixun Dong Jianhua Ran Hong Zhou Jihui Chen Tianluo Lei Weiling Wang Yi Sun Guiting Lin Lise Bankir Baoxue Yang 《PloS one》2013,8(10)
Background
Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line.Methodology/Principal Findings
Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis.Conclusions/Significance
UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders. 相似文献85.
Xiao Li Jianhua Li Yali Tan Dongrui Pan Zhihong Li Xuefeng Yu Juan Yao 《Annals of microbiology》2013,63(4):1247-1256
In this research, we first determined the three most significant nutrient factors affecting haloalcohol dehalogenase HheC production by Escherichia coli P84A/MC1061. These were glycerol, yeast extract, and ammonium sulfate. The steepest ascent method was then applied to obtain the optimal design intervals of the three factors. An application of center composite design was used, and the ingredients of the optimized medium were 1.8 g l?1 glycerol, 48 g l?1 yeast extract, 2.2 g l?1 ammonium sulfate, 5 g l?1 compound phosphate, 1 g l?1 magnesium sulfate, and 1.19?×?10?5?g l?1 ferric sulfate. The enzyme activity reached 109,365 U ml?1 under the most favorable conditions, which is a 277.7 % increase compared with the control group. Our study of cellular respiration parameters (oxygen uptake rate and carbon dioxide emission rate) revealed that the metabolic activity of the strain was strongly promoted under these optimal nutrient conditions and that yeast extract had a positive effect on respiratory intensity and the expression levels of HheC. 相似文献
86.
Wen Fong Ooi Catherine Ong Tannistha Nandi Jason F. Kreisberg Hui Hoon Chua Guangwen Sun Yahua Chen Claudia Mueller Laura Conejero Majid Eshaghi Roy Moh Lik Ang Jianhua Liu Bruno W. Sobral Sunee Korbsrisate Yunn Hwen Gan Richard W. Titball Gregory J. Bancroft Eric Valade Patrick Tan 《PLoS genetics》2013,9(9)
87.
Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia 总被引:1,自引:0,他引:1
Qiang Yu Zhili Guo Xiaofeng Liu Qing Ouyang Cheng He Geoffrey Burnstock Hongbin Yuan Zhenghua Xiang 《Purinergic signalling》2013,9(4):663-675
Transient global ischemia (which closely resembles clinical situations such as cardiac arrest, near drowning or severe systemic hypotension during surgical procedures), often induces delayed neuronal death in the brain, especially in the hippocampal CA1 region. The mechanism of ischemia/reperfusion (I/R) injury is not fully understood. In this study, we have shown that the P2X7 receptor antagonist, BBG, reduced delayed neuronal death in the hippocampal CA1 region after I/R injury; P2X7 receptor expression levels increased before delayed neuronal death after I/R injury; inhibition of the P2X7 receptor reduced I/R-induced microglial microvesicle-like components, IL-1β expression, P38 phosphorylation, and glial activation in hippocampal CA1 region after I/R injury. These results indicate that antagonism of the P2X7 receptor and signaling pathways of microglial MV shedding, such as src-protein tyrosine kinase, P38 MAP kinase and A-SMase, might be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury. 相似文献
88.
89.
Background
Heart failure due to diastolic dysfunction exacts a major economic, morbidity and mortality burden in the United States. Therapeutic agents to improve diastolic dysfunction are limited. It was recently found that Dynamin related protein 1 (Drp1) mediates mitochondrial fission during ischemia/reperfusion (I/R) injury, whereas inhibition of Drp1 decreases myocardial infarct size. We hypothesized that Dynasore, a small noncompetitive dynamin GTPase inhibitor, could have beneficial effects on cardiac physiology during I/R injury.Methods and Results
In Langendorff perfused mouse hearts subjected to I/R (30 minutes of global ischemia followed by 1 hour of reperfusion), pretreatment with 1 µM Dynasore prevented I/R induced elevation of left ventricular end diastolic pressure (LVEDP), indicating a significant and specific lusitropic effect. Dynasore also decreased cardiac troponin I efflux during reperfusion and reduced infarct size. In cultured adult mouse cardiomyocytes subjected to oxidative stress, Dynasore increased cardiomyocyte survival and viability identified by trypan blue exclusion assay and reduced cellular Adenosine triphosphate(ATP) depletion. Moreover, in cultured cells, Dynasore pretreatment protected mitochondrial fragmentation induced by oxidative stress.Conclusion
Dynasore protects cardiac lusitropy and limits cell damage through a mechanism that maintains mitochondrial morphology and intracellular ATP in stressed cells. Mitochondrial protection through an agent such as Dynasore can have clinical benefit by positively influencing the energetics of diastolic dysfunction. 相似文献90.
Ruihan Zhang Xin Li Zhongjie Liang Kongkai Zhu Junyan Lu Xiangqian Kong Sisheng Ouyang Lin Li Yujun George Zheng Cheng Luo 《PloS one》2013,8(8)
Protein arginine methyltransferase 1 (PRMT1), the major arginine asymmetric dimethylation enzyme in mammals, is emerging as a potential drug target for cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1 will facilitate inhibitor design. However, detailed mechanisms of the methyl transfer process and substrate deprotonation of PRMT1 remain unclear. In this study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation by employing molecular dynamics (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) calculation. Ternary complex models, composed of PRMT1, peptide substrate, and S-adenosyl-methionine (AdoMet) as cofactor, were constructed and verified by 30-ns MD simulation. The snapshots selected from the MD trajectory were applied for the QM/MM calculation. The typical SN2-favored transition states of the first and second methyl transfers were identified from the potential energy profile. Deprotonation of substrate arginine occurs immediately after methyl transfer, and the carboxylate group of E144 acts as proton acceptor. Furthermore, natural bond orbital analysis and electrostatic potential calculation showed that E144 facilitates the charge redistribution during the reaction and reduces the energy barrier. In this study, we propose the detailed mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on the small-molecule effectors design, and enables further investigations into the physiological function of this family. 相似文献