全文获取类型
收费全文 | 1817篇 |
免费 | 157篇 |
国内免费 | 186篇 |
专业分类
2160篇 |
出版年
2024年 | 11篇 |
2023年 | 27篇 |
2022年 | 52篇 |
2021年 | 89篇 |
2020年 | 80篇 |
2019年 | 84篇 |
2018年 | 59篇 |
2017年 | 62篇 |
2016年 | 74篇 |
2015年 | 114篇 |
2014年 | 132篇 |
2013年 | 144篇 |
2012年 | 165篇 |
2011年 | 143篇 |
2010年 | 106篇 |
2009年 | 86篇 |
2008年 | 118篇 |
2007年 | 67篇 |
2006年 | 61篇 |
2005年 | 54篇 |
2004年 | 45篇 |
2003年 | 39篇 |
2002年 | 42篇 |
2001年 | 35篇 |
2000年 | 34篇 |
1999年 | 37篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 14篇 |
1995年 | 22篇 |
1994年 | 18篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 14篇 |
1988年 | 14篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1973年 | 1篇 |
1967年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有2160条查询结果,搜索用时 15 毫秒
141.
Erpeng Liu Lei Lv Yonghao Zhan Yuan Ma Jinjin Feng Yulin He Yibo Wen Yanping Zhang Qingsong Pu Fengping Ji Xinghuan Yang Jian Guo Wen 《Journal of cellular and molecular medicine》2021,25(16):7660
Renal fibrosis induced by urinary tract obstruction is a common clinical occurrence; however, effective treatment is lacking, and a deeper understanding of the mechanism of renal fibrosis is needed. Previous studies have revealed that miR‐21 impacts liver and lung fibrosis progression by activating the SPRY1/ERK/NF‐kB signalling pathway. However, whether miR‐21 mediates obstructive renal fibrosis through the same signalling pathway has not been determined. Additionally, studies have shown that N6‐methyladenosine (m6A) modification‐dependent primary microRNA (pri‐microRNA) processing is essential for maturation of microRNAs, but its role in the maturation of miR‐21 in obstructive renal fibrosis has not yet been investigated in detail. To address these issues, we employed a mouse model of unilateral ureteral obstruction (UUO) in which the left ureters were ligated for 3, 7 and 14 days to simulate the fibrotic process. In vitro, human renal proximal tubular epithelial (HK‐2) cells were transfected with plasmids containing the corresponding sequence of METTL3, miR‐21‐5p mimic or miR‐21‐5p inhibitor. We found that the levels of miR‐21‐5p and m6A modification in the UUO model groups increased significantly, and as predicted, the SPRY1/ERK/NF‐kB pathway was activated by miR‐21‐5p, confirming that miR‐21‐5p plays an important role in obstructive renal fibrosis by enhancing inflammation. METTL3 was found to play a major catalytic role in m6A modification in UUO mice and drove obstructive renal fibrosis development by promoting miR‐21‐5p maturation. Our research is the first to demonstrate the role of the METTL3‐m6A‐miR‐21‐5p‐SPRY1/ERK/NF‐kB axis in obstructive renal fibrosis and provides a deeper understanding of renal fibrosis. 相似文献
142.
Pu Hyeon Cha Sun-Yung Park Min-Woo Moon Bindu Subhadra Tae-Kwang Oh Eungbin Kim Jihyun F. Kim Jung-Kee Lee 《Applied microbiology and biotechnology》2010,85(4):1061-1068
Genome analysis of C. glutamicum ATCC 13032 has showed one putative adenylate cyclase gene, cyaB (cg0375) which encodes membrane protein belonging to class III adenylate cyclases. To characterize the function of cyaB, a deletion mutant was constructed, and the mutant showed decreased level of intracellular cyclic AMP compared to that of
wild-type. Interestingly, the cyaB mutant displayed growth defect on acetate medium, and this effect was reversed by complementation with cyaB gene. Similarly, it showed growth defect on glucose-acetate mixture minimal medium, and the utilization of glucose was retarded
in the presence of acetate. The deletion mutant retained the activity of glyoxylate bypass enzymes. Additionally, the mutant
could grow on ethanol but not on propionate medium. The data obtained from this study suggests that adenylate cyclase plays
an essential role in the acetate metabolism of C. glutamicum, even though detailed regulatory mechanisms involving cAMP are not yet clearly defined. The observation that glyoxylate bypass
enzymes are derepressed in cyaB mutant indicates the involvement of cAMP in the repression of aceB and aceA. 相似文献
143.
The time course of enzyme concentrations in metabolic pathways can be predicted on the basis of the optimality criterion of minimizing the time period in which an essential product is generated. This criterion is in line with the widely accepted view that high fitness requires high pathway flux. Here, based on Pontryagin's Maximum Principle, a method is developed to solve the corresponding constrained optimal control problem in an almost exclusively analytical way and, thus, to calculate optimal enzyme profiles, when linear, irreversible rate laws are assumed. Three different problem formulations are considered and the corresponding optimization results are derived. Besides the minimization of transition time, we consider an operation time in which 90% of the substrate has been converted into product. In that case, only the enzyme at the lower end of the pathway rather than all enzymes are active in the last phase. In all cases, biphasic or multiphasic time courses are obtained. The biological meaning of the results in terms of a consecutive just-in-time expression of metabolic genes is discussed. For the special case of two-enzyme systems, the role of the Golden section in the solution is outlined. 相似文献
144.
Artur Mikiciński Piotr Sobiczewski Monika Sulikowska Joanna Puławska Jadwiga Treder 《Journal of Phytopathology》2010,158(4):201-209
Soft rot is the most important disease on calla lily in Poland. The isolation of the presumptive pathogen from symptomatic tubers on nutrient agar yielded bacteria with different colony morphology. Of 41 isolates collected, 10 showed pectolytic activity on crystal violet pectate medium and caused soft rot on potato slices. All pectolytic bacteria appeared to be Gram‐negative rods producing typical soft rot on inoculated leaf petioles of calla lily. Bacteria with colonies which morphologically resembled those used for inoculation were re‐isolated from diseased petioles. Their identification was based on phenotypic characters and sequence of the gene fragment coding 16S rRNA. It was found that, in addition to Pectobacterium carotovorum subsp. carotovorum, soft rot of calla lily can be caused by Pectobacterium carotovorum subsp. atrosepticum, Pseudomonas marginalis, Pseudomonas veronii and Chryseobacterium indologenes. The latter two are described for the first time as plant pathogens. The pectolytic activity of all identified bacteria, except that of P. carotovorum subsp. atrosepticum, was lower than that of P. carotovorum subsp. carotovorum, but strains of P. veronii showed a higher activity than P. marginalisand C. indologenes species. 相似文献
145.
Nick Fenby Hong Pu Roger Pennell Uta Praekelt Rob Day Rod Scott 《Sexual plant reproduction》2010,23(4):255-264
Simple de novo screens in Arabidopsis thaliana have previously identified mutants that affect endosperm development but viable-embryo mutants have not been identified.
Our strategy to identify autonomous embryo development was to uncouple embryo and endosperm fertilisation. This involved a
male-sterile mutant population being crossed with a distinct pollen parent—the pollen was needed to initiate endosperm development
and because it was distinct, the maternal progeny could be selected from the hybrid population. This process was refined over
three stages, resulting in a viable approach to screen for autonomous embryo mutants. From 8,000 screened plants, a mutation
was isolated in which the integument cells extended from the ovule and proliferated into a second complete twinned ovule.
Some embryos from the mutant were normal but others developed fused cotyledons. In addition, a proportion of the progeny lacked
paternal genes. 相似文献
146.
Objective: We needed to establish an embryonic fibroblast cell line from the Langshan chicken (LSCEF61) to preserve their important genetic resources at the cellular level. Material and methods: The cell line was established from 9‐day‐old embryos by direct explant culture and cryopreservation techniques. Cell morphology, dynamic proliferation and any contamination present were tested, and the karyotype and levels of isoenzymes of lactic dehydrogenase and malic dehydrogenase were analysed. Four types of fluorescent protein exogenous genes for pEGFP‐C1, pEGFP‐N3, pEYFP‐N1 and pDsRed1‐N1 were transfected into the cells. Results: Showed that the cells were healthy and were of spindle shaped structure, without change in morphology. Cell growth curves were of typical S‐shape. Assays for microbial contamination were negative. The LSCEF61 line showed no cross‐contamination when assessed by isoenzyme analysis. Chromosome number (2n) = 78 on more than 90% of occasions. The four types of fluorescent protein extro‐genes appeared to be expressed effectively with high transfection efficiency between 15.6% and 38.6%. Conclusion: The cell line met each of the quality control standards required for the American Type Culture Collection. It had not only preserved the genetic resources of the important Langshan chicken at the cellular level, but also provided valuable material for genomic, post‐genomic and somatic cell cloning research and other applications. 相似文献
147.
Vinod R. Hegde Scott Borges Haiyan Pu Mahesh Patel Vincent P. Gullo Bonnie Wu Paul Kirschmeier Michael J. Williams Vincent Madison Thierry Fischmann Tze-Ming Chan 《Bioorganic & medicinal chemistry letters》2010,20(4):1384-1387
Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. The study helped to derive some conclusions about the structure–activity relation around the phenanthrin moiety. Semi-synthetic aristolactam 21 showed good activity with inhibition IC50 of 35 nM in CDK2 assay. The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature. 相似文献
148.
Chun-Nan Lin A-Mei Huang Kai-Wei Lin Tzyh-Chyuan Hour Horng-Huey Ko Shyh-Chyun Yang Yeong-Shiau Pu 《Phytochemistry》2010,71(17-18):2140-2146
The diterpenoids (+)-ferruginol (1), ent-kaur-16-en-15-one (2), ent-8(14),15-sandaracopimaradiene-2α,18-diol (3), 8(14),15-sandaracopimaradiene-2α,18,19-triol (4), and (+)-sugiol (5) and the triterpenoids 3β-methoxycycloartan-24(241)-ene (6), 3β,23β-dimethoxycycloartan-24(241)-ene (7), 3β,23β-dimethoxy-5α-lanosta-24(241)-ene (8), and 23(S)-23-methoxy-24-methylenelanosta-8-en-3-one (9), isolated from Amentotaxus formosana, showed inhibitory effects on xanthine oxidase (XO). Of the compounds tested, compound 5 was a potent inhibitor of XO activity, with an IC50 value of 6.8 ± 0.4 μM, while displaying weak ABTS radical cation scavenging activity. Treatment of the bladder cancer cell line, NTUB1, with 3–10 μM of compound 5 and 10 μM cisplatin, and immortalized normal human urothelial cell line, SV-HUC1, with 0.3–1 μM and 10–50 μM of compound 5 and 10 μM cisplatin, respectively, resulted in increased viability of cells compared with cytotoxicity induced by cisplatin. Treatment of NTUB1 with 20 μM cisplatin and 10 or 30 μM of compound 5 resulted in decreased ROS production compared with ROS production induced by cisplatin. These results indicate that 10 or 30 μM of compound 5 in NTUB1 cells may mediate through the suppression of XO activity and reduction of reactive oxygen species (ROS) induced by compound 5 cotreated with 20 μM cisplatin and protection of subsequent cell death. 相似文献
149.
150.
Luis Gracia Elena Ibarz Sergio Puértolas José Cegoñino Fernando López-Prats Juan J Panisello Antonio Herrera 《Biomedical engineering online》2010,9(1):22