全文获取类型
收费全文 | 9494篇 |
免费 | 714篇 |
国内免费 | 825篇 |
专业分类
11033篇 |
出版年
2024年 | 19篇 |
2023年 | 134篇 |
2022年 | 305篇 |
2021年 | 517篇 |
2020年 | 324篇 |
2019年 | 453篇 |
2018年 | 417篇 |
2017年 | 261篇 |
2016年 | 439篇 |
2015年 | 614篇 |
2014年 | 720篇 |
2013年 | 816篇 |
2012年 | 910篇 |
2011年 | 797篇 |
2010年 | 455篇 |
2009年 | 462篇 |
2008年 | 471篇 |
2007年 | 414篇 |
2006年 | 372篇 |
2005年 | 272篇 |
2004年 | 261篇 |
2003年 | 214篇 |
2002年 | 161篇 |
2001年 | 135篇 |
2000年 | 127篇 |
1999年 | 108篇 |
1998年 | 100篇 |
1997年 | 95篇 |
1996年 | 89篇 |
1995年 | 75篇 |
1994年 | 65篇 |
1993年 | 48篇 |
1992年 | 78篇 |
1991年 | 47篇 |
1990年 | 33篇 |
1989年 | 37篇 |
1988年 | 22篇 |
1987年 | 25篇 |
1986年 | 25篇 |
1985年 | 24篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 9篇 |
1976年 | 4篇 |
1973年 | 5篇 |
1971年 | 4篇 |
1968年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
Xiaoxia Xue Zhihua Yin Yao Lu Haibo Zhang Ying Yan Yuxia Zhao Xuelian Li Zeshi Cui Miao Yu Lu Yao Baosen Zhou 《PloS one》2013,8(8)
Background
The human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes play an important role in the DNA base excision repair pathway. Single nucleotide polymorphisms (SNPs) in critical genes are suspected to be associated with the risk of lung cancer. This study aimed to identify the association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female population, and investigated the interaction between genetic polymorphisms and environmental exposure in lung adenocarcinoma.Methods
We performed a hospital-based case-control study, including 410 lung adenocarcinoma patients and 410 cancer-free hospital control subjects who were matched for age. Each case and control was interviewed to collect information by well-trained interviewers. A total of 10 ml of venous blood was collected for genotype testing. Three polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique.Results
We found that individuals who were homozygous for the variant hOGG1 326Cys/Cys showed a significantly increased risk of lung adenocarcinoma (OR = 1.54; 95% CI: 1.01–2.36; P = 0.045). When the combined effect of variant alleles was analyzed, we found an increased OR of 1.89 (95% CI: 1.24–2.88, P = 0.003) for lung adenocarcinoma individuals with more than one homozygous variant allele. In stratified analyses, we found that the OR for the gene-environment interaction between Ser/Cys and Cys/Cys genotypes of hOGG1 codon 326 and cooking oil fumes for the risk of lung adenocarcinoma was 1.37 (95% CI: 0.77–2.44; P = 0.279) and 2.79 (95% CI: 1.50–5.18; P = 0.001), respectively.Conclusions
The hOGG1 Ser326Cys polymorphism might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, there is a significant gene-environment association between cooking oil fumes and hOGG1 326 Cys/Cys genotype in lung adenocarcinoma among female non-smokers. 相似文献102.
Wei Li Jing Wang Qiu-Dan Chen Xu Qian Qi Li Yu Yin Zhu-Mei Shi Lin Wang Jie Lin Ling-Zhi Liu Bing-Hua Jiang 《PloS one》2013,8(6)
Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1α and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1α expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1α inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the role and mechanism ofinsulin in regulating glycolytic activities via miR-99a/mTOR. 相似文献
103.
Jing Zhang Mingjian Zhou Zhenglin Ge Jie Shen Can Zhou Cecilia Gotor Luis C. Romero Xingliang Duan Xin Liu Deliang Wu Xianchao Yin Yanjie Xie 《Plant, cell & environment》2020,43(3):624-636
Recent studies have demonstrated that hydrogen sulfide (H2S) produced through the activity of l -cysteine desulfhydrase (DES1) is an important gaseous signaling molecule in plants that could participate in abscisic acid (ABA)-induced stomatal closure. However, the coupling of the DES1/H2S signaling pathways to guard cell movement has not been thoroughly elucidated. The results presented here provide genetic evidence for a physiologically relevant signaling pathway that governs guard cell in situ DES1/H2S function in stomatal closure. We discovered that ABA-activated DES1 produces H2S in guard cells. The impaired guard cell ABA phenotype of the des1 mutant can be fully complemented when DES1/H2S function has been specifically rescued in guard cells and epidermal cells, but not mesophyll cells. This research further characterized DES1/H2S function in the regulation of LONG HYPOCOTYL1 (HY1, a member of the heme oxygenase family) signaling. ABA-induced DES1 expression and H2S production are hyper-activated in the hy1 mutant, both of which can be fully abolished by the addition of H2S scavenger. Impaired guard cell ABA phenotype of des1/hy1 can be restored by H2S donors. Taken together, this research indicated that guard cell in situ DES1 function is involved in ABA-induced stomatal closure, which also acts as a pivotal hub in regulating HY1 signaling. 相似文献
104.
Yin Yulin Zhang Peijun Liu Jia Wang Nan Shang Xinchi Zhang Yilin Li Yuehong 《Biological trace element research》2020,194(2):552-559
Biological Trace Element Research - Cadmium (Cd) is the most common heavy metal and is easily detected in aquatic environments on a global scale. Vitamin C was a widely used vitamin in aquaculture.... 相似文献
105.
Shang-Ling Xiong Gyu Tae Lim Shang-Jun Yin Jinhyuk Lee Jae-Rin Lee Myong-Joon Hahn 《Journal of biomolecular structure & dynamics》2020,38(12):3496-3503
AbstractThe inhibition of α-glucosidase is used as a key clinical approach to treat type 2 diabetes mellitus and thus, we assessed the inhibitory effect of α-ketoglutaric acid (AKG) on α-glucosidase with both an enzyme kinetic assay and computational simulations. AKG bound to the active site and interacted with several key residues, including ASP68, PHE157, PHE177, PHE311, ARG312, TYR313, ASN412, ILE434 and ARG439, as detected by protein–ligand docking and molecular dynamics simulations. Subsequently, we confirmed the action of AKG on α-glucosidase as mixed-type inhibition with reversible and rapid binding. The relevant kinetic parameter IC50 was measured (IC50 = 1.738?±?0.041?mM), and the dissociation constant was determined (Ki Slope = 0.46?±?0.04?mM). Regarding the relationship between structure and activity, a high AKG concentration induced the slight modulation of the shape of the active site, as monitored by hydrophobic exposure. This tertiary conformational change was linked to AKG inhibition and mostly involved regional changes in the active site. Our study provides insight into the functional role of AKG due to its structural property of a hydroxyphenyl ring that interacts with the active site. We suggest that similar hydroxyphenyl ring-containing compounds targeting key residues in the active site might be potential α-glucosidase inhibitors. Abbreviations AKG alpha-ketoglutaric acid pNPG 4-nitrophenyl-α-d-glucopyranoside ANS 1-anilinonaphthalene-8-sulfonate MD molecular dynamics. Communicated by Ramaswamy H. Sarma 相似文献
106.
Yin Wenchao Wang Chunyan Peng Yue Yuan Wenlin Zhang Zhongjun Liu Hong Xia Zhengyuan Ren Congcai Qian Jinqiao 《Molecular biology reports》2020,47(5):3629-3639
Molecular Biology Reports - Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has... 相似文献
107.
Radiation and Environmental Biophysics - Objective of the present study was to investigate the tolerant radiation dose of nasal mucosa by observing and analyzing patients who received... 相似文献
108.
Huang Jiang-Hu Fu Chun-Hui Xu Yang Yin Xiao-Ming Cao Yong Lin Fei-Yue 《Neurochemical research》2020,45(4):760-771
Neurochemical Research - Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome... 相似文献
109.
AbstractBiodegradable polymers are promising binders and carriers for natural antifoulants. In the present study, an antifouling (AF) coating was developed by adding a non-toxic AF compound (butenolide) to a bio-based and biodegradable poly(lactic acid)-based polyurethane. Mass loss measurement showed that the polymer degraded in seawater at a rate of 0.013?mg cm?2?day?1. Measurements showed that butenolide was released from the coatings into seawater over a period of at least three months. Both the concentration of butenolide in the coatings and the ambient temperature determined the release rate of butenolide. The results further demonstrate that incorporating rosin into the coatings increase the self-renewal rate of the polymer and facilitated the long-term release of butenolide from the coating. The results show that poly(lactic acid)-based polyurethane is a suitable polymer for butenolide-based AF coatings. 相似文献
110.
Holliday junction (HJ) resolvases are structure-specific endonucleases that cleave four-way DNA junctions (HJs) generated during DNA recombination and repair. Bacterial RuvC, a prototypical HJ resolvase, functions as homodimer and nicks DNA strands precisely across the junction point. To gain insights into the mechanisms underlying symmetrical strand cleavages by RuvC, we performed crystallographic and biochemical analyses of RuvC from Thermus thermophilus (T.th. RuvC). The crystal structure of T.th. RuvC shows an overall protein fold similar to that of Escherichia coli RuvC, but T.th. RuvC has a more tightly associated dimer interface possibly reflecting its thermostability. The binding mode of a HJ-DNA substrate can be inferred from the shape/charge complementarity between the T.th. RuvC dimer and HJ-DNA, as well as positions of sulfate ions bound on the protein surface. Unexpectedly, the structure of T.th. RuvC homodimer refined at 1.28 Å resolution shows distinct asymmetry near the dimer interface, in the region harboring catalytically important aromatic residues. The observation suggests that the T.th. RuvC homodimer interconverts between two asymmetric conformations, with alternating subunits switched on for DNA strand cleavage. This model provides a structural basis for the ‘nick-counter-nick’ mechanism in HJ resolution, a mode of HJ processing shared by prokaryotic and eukaryotic HJ resolvases. 相似文献