全文获取类型
收费全文 | 22593篇 |
免费 | 1990篇 |
国内免费 | 2678篇 |
出版年
2024年 | 55篇 |
2023年 | 383篇 |
2022年 | 675篇 |
2021年 | 1313篇 |
2020年 | 1011篇 |
2019年 | 1242篇 |
2018年 | 1117篇 |
2017年 | 813篇 |
2016年 | 1098篇 |
2015年 | 1520篇 |
2014年 | 1795篇 |
2013年 | 1854篇 |
2012年 | 2206篇 |
2011年 | 1994篇 |
2010年 | 1250篇 |
2009年 | 1044篇 |
2008年 | 1153篇 |
2007年 | 1043篇 |
2006年 | 882篇 |
2005年 | 726篇 |
2004年 | 619篇 |
2003年 | 504篇 |
2002年 | 435篇 |
2001年 | 342篇 |
2000年 | 296篇 |
1999年 | 263篇 |
1998年 | 192篇 |
1997年 | 167篇 |
1996年 | 195篇 |
1995年 | 159篇 |
1994年 | 137篇 |
1993年 | 93篇 |
1992年 | 127篇 |
1991年 | 87篇 |
1990年 | 88篇 |
1989年 | 71篇 |
1988年 | 59篇 |
1987年 | 43篇 |
1986年 | 40篇 |
1985年 | 47篇 |
1984年 | 21篇 |
1983年 | 21篇 |
1982年 | 18篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1971年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 592 毫秒
991.
PAQR3 controls autophagy by integrating AMPK signaling to enhance ATG14L‐associated PI3K activity
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Da‐Qian Xu Zheng Wang Chen‐Yao Wang De‐Yi Zhang Hui‐Da Wan Zi‐Long Zhao Jin Gu Yong‐Xian Zhang Zhi‐Gang Li Kai‐Yang Man Yi Pan Zhi‐Fei Wang Zun‐Ji Ke Zhi‐Xue Liu Lu‐Jian Liao Yan Chen 《The EMBO journal》2016,35(5):496-514
The Beclin1–VPS34 complex is recognized as a central node in regulating autophagy via interacting with diverse molecules such as ATG14L for autophagy initiation and UVRAG for autophagosome maturation. However, the underlying molecular mechanism that coordinates the timely activation of VPS34 complex is poorly understood. Here, we identify that PAQR3 governs the preferential formation and activation of ATG14L‐linked VPS34 complex for autophagy initiation via two levels of regulation. Firstly, PAQR3 functions as a scaffold protein that facilitates the formation of ATG14L‐ but not UVRAG‐linked VPS34 complex, leading to elevated capacity of PI(3)P generation ahead of starvation signals. Secondly, AMPK phosphorylates PAQR3 at threonine 32 and switches on PI(3)P production to initiate autophagosome formation swiftly after glucose starvation. Deletion of PAQR3 leads to reduction of exercise‐induced autophagy in mice, accompanied by a certain degree of disaggregation of ATG14L‐associated VPS34 complex. Together, this study uncovers that PAQR3 can not only enhance the capacity of pro‐autophagy class III PI3K due to its scaffold function, but also integrate AMPK signal to activation of ATG14L‐linked VPS34 complex upon glucose starvation. 相似文献
992.
Yin Chen Wen-Jun Mao Meng-Xia Yan Xue Liu Shu-Yao Wang Zheng Xia Bo Xiao Su-Jian Cao Bao-Qin Yang Jie Li 《Marine biotechnology (New York, N.Y.)》2016,18(3):301-313
Marine sponges are ancient and simple multicellular filter-feeding invertebrates attached to solid substrates in benthic habitats and host a variety of fungi both inside and on their surface because of its unique ingestion and digest system. Investigation on marine sponge-associated fungi mainly focused on the small molecular metabolites, yet little attention had been paid to the extracellular polysaccharides. In this study, a homogeneous extracellular polysaccharide AS2-1 was obtained from the fermented broth of the marine sponge endogenous fungus Alternaria sp. SP-32 using ethanol precipitation, anion-exchange, and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that AS2-1 was composed of mannose, glucose, and galactose with a molar ratio of 1.00:0.67:0.35, and its molecular weight was 27.4 kDa. AS2-1 consists of a mannan core and a galactoglucan chain. The mannan core is composed of (1→6)-α-Manp substituted at C-2 by (1→2)-α-Manp with different degrees of polymerization. The galactoglucan chain consists of (1→6)-α-Glcp residues with (1→6)-β-Galf residues attached to the last glucopyranose residue at C-6. (1→6)-β-Galf residues have additional branches at C-2 consisting of disaccharide units of (1→2)-β-Galf and (1→2)-α-Glcp residues. The glucopyranose residue of the galactoglucan chain is linked to the mannan core. AS2-1 possessed a high antioxidant activity as evaluated by scavenging of 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals in vitro. AS2-1 was also evaluated for cytotoxic activity on Hela, HL-60, and K562 cell lines by the MTT and SRB methods. The investigation demonstrated that AS2-1 was a novel extracellular polysaccharide with different characterization from extracellular polysaccharides produced by other marine microorganisms. 相似文献
993.
Min Cai Yulong Ma Wei Zhang Shiquan Wang Ying Wang Li Tian Zhengwu Peng Huaning Wang Tan Qingrong 《International journal of biological sciences》2016,12(1):42-52
Stroke is the major cause of permanent disability and mortality in China. Apigenin-7-O-β-D-(-6''''-p-coumaroyl)-glucopyranoside (APG) is a glycoside subtype of apigenin and has the antioxidant activity; however, whether and how it plays a neuroprotective role following cerebral ischemia remains unknown. In present study, we adopted the oxygen glucose/reperfusion model in PC12 cells, bilateral common carotid artery occlusion model in C57B6 mice and middle cerebral artery occlusion model in SD rats to observe the therapeutic effects of APG on ischemic stroke. We also discussed the underlying mechanism. Treatment with 0.4 μg/ml or 0.8 μg/ml APG promoted cell viability and proliferation, reduced LDH release and apoptotic cell death levels in PC12 cells. Treatment with 50 mg/kg or 100 mg/kg APG at 30 minutes after reperfusion improved neurological outcomes in vivo, as demonstrated by elevation of neurological scores in both mice and rats. It also increased the number of survival neurons in mice and reduced infarct volume in rats. APG also increased the contents of Mn-SOD and the phosphorylation level of STAT3, elevated the antioxidant activity and reduced oxidative productions. These findings revealed a neuroprotective effect of APG, which possibly induced by the STAT3 phosphorylation-mediated Mn-SOD up-regulation. 相似文献
994.
995.
Manuel J. Steinbauer Richard Field John‐Arvid Grytnes Panayiotis Trigas Claudine Ah‐Peng Fabio Attorre H. John B. Birks Paulo A. V. Borges Pedro Cardoso Chang‐Hung Chou Michele De Sanctis Miguel M. de Sequeira Maria C. Duarte Rui B. Elias José María Fernández‐Palacios Rosalina Gabriel Roy E. Gereau Rosemary G. Gillespie Josef Greimler David E. V. Harter Tsurng‐Juhn Huang Severin D. H. Irl Daniel Jeanmonod Anke Jentsch Alistair S. Jump Christoph Kueffer Sandra Nogué Rüdiger Otto Jonathan Price Maria M. Romeiras Dominique Strasberg Tod Stuessy Jens‐Christian Svenning Ole R. Vetaas Carl Beierkuhnlein 《Global Ecology and Biogeography》2016,25(9):1097-1107
996.
997.
Mei Wang Xinxin Lu Ailian Hu Mingxin Zhang Xue Li Shijing Deng Ningli Wang 《中国科学:生命科学英文版》2016,59(6):555-560
The aim of this study was to investigate the etiological characteristics of Chlamydia trachomatis conjunctivitis among resident students at primary schools in the Qinghai Tibetan area in order to understand the distribution of C. trachomatis and other pathogenic microorganisms, to detect the isolation rate of infectious pathogens, and to provide an evidence for further targeted efforts in the prevent of sporadic trachoma efforts. From two primary schools in Qinghai Province, ocular samples from 35 students who were clinically diagnosed as trachoma cases and 60 normal controls were obtained by swabbing their upper eyelids and lower conjunctival sacs. Samples were preserved at 4°C and airlifted to Beijing Tongren Hospital within 24 h. Real-time polymerase chain reaction(RT-PCR) was used to screen for C. trachomatis, and nested PCR was used to amplify a fragment of the omp A gene for serotype confirmation. Bacterial cultivation and sensitivity tests were conducted based on the 2015 version of the Clinical and Laboratory Standards Institute. Adenovirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were screened by RT-PCR. Among the 35 students with trachoma, 8 came from the Jianshetang Primary School and 27 came from the Central Primary School. Two novel C. trachomatis B serotypes(Gen Bank accession numbers KU737520 and KU737521) were detected based on a sequence analysis of the omp A gene. Single C. trachomatis infections accounted for 42.86%(9/21) of the cases, and infections with multiple bacteria, particularly Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniae, accounted for the remaining 57.14%(12/21). Of the 14 C. trachomatis-negative samples, one was positive for adenoviral infection(serotype D) and 13 were positive for bacterial infections(H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, streptococci other than S. pneumoniae, Staphylococcus epidermidis, Corynebacterium, and Arthrobacterium). In addition to C. trachomatis, the other bacteria and virus that were detected in the boarding students of primary schools in the Qinghai Tibetan area should be emphasized in trachoma prevention and control. 相似文献
998.
Xue Li Shaoya Zhang Qingfeng Liang Mei Wang Ailian Hu Xiuyuan Li Benshan Yang Mingxin Zhang Ningli Wang Xinxin Lu 《中国科学:生命科学英文版》2016,59(6):561-570
To study the molecular characteristics of Chlamydia trachomatis, the major outer membrane protein gene(omp A) of C. trachomatis from primary school students with trachoma residing in the Qinghai Tibetan area was sequenced and compared with the same serotype in Gen Bank. In Jianshetang Primary School and Galeng Central Primary School in the Galeng Tibetan Township of Qinghai Haidong Sala Autonomous County, scraped samples were collected from the upper tarsal conjunctiva and lower conjunctival sac of both eyes of 45 students with trachoma, stored at 4°C, and transported to Beijing Tongren Hospital by air within 24 h. The samples were screened for C. trachomatis by real-time PCR. The omp A gene from the C. trachomatis-positive samples was amplified by nested PCR. The serotype was confirmed by National Center for Biotechnology Information(NCBI) BLAST search and homology analysis. The entire omp A gene sequence was compared with the corresponding gene sequences of serotype B strains available in Gen Bank. Of the 45 students aged 6–13 years with trachoma, 26 C. trachomatis-positive students were identified by the initial real-time PCR screening(average age,(9.09±1.63) years; sex ratio, 1.0), accounting for 57.78%(26/45). The cycle threshold values for real-time PCR were 16.79–37.77. Half(13/26) of C. trachomatis-positive students had a bacterial copy number of 105. The compliance rate of the omp A gene sequences with the C. trachomatis serotype B strains in Gen Bank was up to 99%. Two novel genetic mutations were found when the omp A gene was compared with those of the 11 serotype B strains in Gen Bank. The two non-synonymous mutations were located at(i) position 271 in the second constant domain, an adenine(A) to guanine(G) substitution(ACT?GCT), changing the amino acid at position 91 from threonine to alanine(Thr?Ala) in all 26 strains; and(ii) position 887 in the fourth variable domain, a cytosine(C) to thymine(T) substitution(GCA?GTA), changing the amino acid at residue 296 from alanine to valine(Ala?Val) in four of the 26 strains. Six mutations were identified relative to ATCC VR-573. The strains could be divided into two gene clusters according to the mutation at nucleotide position 887: CQZ-1(China Qinghai Tibetan-1) and CQZ-2(China Qinghai Tibetan-2). We thus detected two novel serotype B mutant strains of C. trachomatis among study subjects with trachoma. 相似文献
999.
1000.
Shengguo Xue Feng Zhu Jie Lei William Hartley Weisong Pan 《International journal of phytoremediation》2016,18(7):710-719
Chenopodium ambrosioides L. can tolerate high concentrations of manganese and has potential for its use in the revegetation of manganese mine tailings. Following a hydroponic investigation, transmission electron microscopy (TEM)-energy disperse spectroscopy (EDS) was used to study microstructure changes and the possible accumulation of Mn in leaf cells of C. ambrosioides in different Mn treatments (200, 1000, 10000 μmol·L?1). At 200 μmol·L?1, the ultrastructure of C. ambrosioides was clearly visible without any obvious damage. At 1000 μmol·L?1, the root, stem and leaf cells remained intact, and the organelles were clearly visible without any obvious damage. However, when the Mn concentration exceeded 1000 μmol·L?1 the number of mitochondria in root cells decreased and the chloroplasts in stem cells showed a decrease in grana lamellae and osmiophilic granules. Compared to controls, treatment with 1000 μmol·L?1 or 10000 μmol·L?1 Mn over 30 days, gave rise to black agglomerations in the cells. At 10000 μmol·L?1, Mn was observed to form acicular structures in leaf cells and intercellular spaces, which may be a form of tolerance and accumulation of Mn in C. ambrosioides. This study has furthered the understanding of Mn tolerance mechanisms in plants, and is potential for the revegetation of Mn-polluted soils. 相似文献