全文获取类型
收费全文 | 5307篇 |
免费 | 520篇 |
国内免费 | 212篇 |
出版年
2023年 | 49篇 |
2022年 | 120篇 |
2021年 | 192篇 |
2020年 | 128篇 |
2019年 | 144篇 |
2018年 | 152篇 |
2017年 | 99篇 |
2016年 | 171篇 |
2015年 | 284篇 |
2014年 | 296篇 |
2013年 | 357篇 |
2012年 | 392篇 |
2011年 | 382篇 |
2010年 | 245篇 |
2009年 | 206篇 |
2008年 | 259篇 |
2007年 | 229篇 |
2006年 | 254篇 |
2005年 | 191篇 |
2004年 | 205篇 |
2003年 | 151篇 |
2002年 | 133篇 |
2001年 | 107篇 |
2000年 | 109篇 |
1999年 | 97篇 |
1998年 | 40篇 |
1997年 | 44篇 |
1996年 | 40篇 |
1995年 | 36篇 |
1994年 | 43篇 |
1993年 | 41篇 |
1992年 | 66篇 |
1991年 | 74篇 |
1990年 | 47篇 |
1989年 | 57篇 |
1988年 | 57篇 |
1987年 | 55篇 |
1986年 | 46篇 |
1985年 | 55篇 |
1984年 | 43篇 |
1983年 | 31篇 |
1982年 | 23篇 |
1981年 | 20篇 |
1979年 | 31篇 |
1978年 | 23篇 |
1977年 | 18篇 |
1975年 | 21篇 |
1974年 | 22篇 |
1973年 | 25篇 |
1971年 | 17篇 |
排序方式: 共有6039条查询结果,搜索用时 15 毫秒
991.
Chu F Ren X Chasse A Hickman T Zhang L Yuh J Smith MT Burlingame AL 《Chemico-biological interactions》2011,192(1-2):113-117
Recent studies reveal that posttranslational modifications on chromatin proteins, especially histones, organize genomic DNA and mediate various cellular responses to environmental influences. Quantitative mass spectrometric analysis is a powerful approach to reveal these dynamic events on chromatin in a systematic manner. Here, the effects of arsenic exposure on histone epigenetic state were investigated in human UROtsa cells, and a reduction in acetylation level on several histone H3 and H4 lysine residues was detected. Furthermore, MYST1 was shown to be the major histone acetyltransferase for H4 Lys16 and protect UROtsa cells from arsenic toxicity. 相似文献
992.
993.
Lin CC Chu CF Liu PH Lin HH Liang SC Hsu WE Lin JS Wang HM Chang LL Chien CT Jeng ST 《Plant & cell physiology》2011,52(2):421-435
The involvement of lipase in flowering is seldom studied, and this research provides evidence that fatty acids produced by lipase affect flowering. OSAG78 encoding a patatin-like protein was isolated from Oncidium Gower Ramsey. OSAG78 fused with green fluorescent protein was found to localize at the cell membrane. Transgenic Arabidopsis overexpressing OSAG78 demonstrated higher lipase activity than the wild-type control. In addition, the amount of free linoleic acid and linolenic acid in transgenic Arabidopsis was found to be higher than that in the wild type. Transgenics overexpressing OSAG78 exhibited altered phenotypes, including smaller leaves and rounder flowers, and also demonstrated a late flowering phenotype that could be rescued by gibberellin A(3) (GA(3)) application. Several flowering-related genes were analyzed, indicating that the expression of gibberellin-stimulated genes was decreased in the plants overexpressing OSAG78. Also, the expression of AtGA2ox1, AtGA3ox1 and AtGA20ox1 genes encoding GA2-, GA3- and GA20-oxidases, respectively, which are mainly responsible for gibberellin metabolism, was decreased, and the level of GA(4), a bioactive gibberellin, measured by gas chromatography-mass spectrometry was also reduced in the overexpressing lines. Furthermore, the expression levels of AtGA3ox1 and AtGA20ox1 were significantly decreased in wild-type Arabidopsis treated with linoleic acid, linolenic acid or methyl jasmonate. The membrane-bound OSAG78 might hydrolyze phospholipids to release linoleic acid and linolenic acid, and then depress the expression of genes encoding GA3- and GA20-oxidase. These changes reduced the bioactive gibberellin level, and, finally, late flowering occurred. Our results indicate that a patatin-like membrane protein with lipase activity affects flowering through the regulation of gibberellin metabolism. 相似文献
994.
Tarocystatin (CeCPI) from taro (Colocasia esculenta cv. Kaohsiung no. 1), a group-2 phytocystatin, shares a conserved N-terminal cystatin domain (NtD) with other phytocystatins but contains a C-terminal cystatin-like extension (CtE). The structure of the tarocystatin–papain complex and the domain interaction between NtD and CtE in tarocystatin have not been determined. We resolved the crystal structure of the phytocystatin–papain complex at resolution 2.03 Å. Surprisingly, the structure of the NtD–papain complex in a stoichiometry of 1:1 could be built, with no CtE observed. Only two remnant residues of CtE could be built in the structure of the CtE–papain complex. Therefore, CtE is easily digested by papain. To further characterize the interaction between NtD and CtE, three segments of tarocystatin, including the full-length (FL), NtD and CtE, were used to analyze the domain–domain interaction and the inhibition ability. The results from glutaraldehyde cross-linking and yeast two-hybrid assay indicated the existence of an intrinsic flexibility in the region linking NtD and CtE for most tarocystatin molecules. In the inhibition activity assay, the glutathione-S-transferase (GST)-fused FL showed the highest inhibition ability without residual peptidase activity, and GST-NtD and FL showed almost the same inhibition ability, which was higher than with NtD alone. On the basis of the structures, the linker flexibility and inhibition activity of tarocystatins, we propose that the overhangs from the cystatin domain may enhance the inhibition ability of the cystatin domain against papain. 相似文献
995.
996.
Liskovykh MA Chuĭkin IA Ranjan A Safina DA Tolkunova EN Minina IuM Zhdanova NS Dyban PA Mullins J Kostyleva EI Chikhirzhina EV Bader M Alenina N Tomilin AN 《Tsitologiia》2011,53(12):939-945
The rat represents very important, superior in many respects to the mous, animal model for studying pharmacology, physiology, ageing, cardiovascular etc. However, numerous attempts to derive rat ES cells necessary to carry out loss-of-gene-function studies have not been successful thus far. Therefore rat induct pluripotent stem cells (or riPS) should provide a notable alternative to ES cell, allowing to study gene functions in this valuable animal model. Here we report an improved lentivirus-based riPS derivation protocol that makes use of small inhibitors of MEK and GSK3. We show that the excision of proviruses does not affect neither karyotype and pluripotency state of these cells. Also, we propose genetic tool for an improvement of the quality of riPS cells in culture. These data may prompt further iPS-based gene targeting in rat as well as the development iPS-based gene therapies, using this animal model. 相似文献
997.
998.
Tang Z Xiao C Zhuang Y Chu J Zhang S Herron PR Hunter IS Guo M 《Enzyme and microbial technology》2011,49(1):17-24
The aromatic polyketide antibiotic, oxytetracycline (OTC), is produced by Streptomyces rimosus as an important secondary metabolite. High level production of antibiotics in Streptomycetes requires precursors and cofactors which are derived from primary metabolism; therefore it is exigent to engineer the primary metabolism. This has been demonstrated by targeting a key enzyme in the oxidative pentose phosphate pathway (PPP) and nicotinamide adenine dinucleotide phosphate (NADPH) generation, glucose-6-phosphate dehydrogenase (G6PDH), which is encoded by zwf1 and zwf2. Disruption of zwf1 or zwf2 resulted in a higher production of OTC. The disrupted strain had an increased carbon flux through glycolysis and a decreased carbon flux through PPP, as measured by the enzyme activities of G6PDH and phosphoglucose isomerase (PGI), and by the levels of ATP, which establishes G6PDH as a key player in determining carbon flux distribution. The increased production of OTC appeared to be largely due to the generation of more malonyl-CoA, one of the OTC precursors, as observed in the disrupted mutants. We have studied the effect of zwf modification on metabolite levels, gene expression, and secondary metabolite production to gain greater insight into flux distribution and the link between the fluxes in the primary and secondary metabolisms. 相似文献
999.
Lin PR Tsai HP Tsui PY Weng MH Kuo MD Lin HC Chen KC Ji DD Chu DM Liu WT 《Applied and environmental microbiology》2011,77(10):3398-3405
Orientia tsutsugamushi is the etiological agent of scrub typhus, a mite-borne, febrile illness that occurs in the Asia-Pacific region. We conducted strain characterization of O. tsutsugamushi isolates from chiggers obtained from rodents based the nucleotide sequence of the 56-kDa outer membrane protein gene. With the use of PCR, a total of 68 DNA sequences of 56-kDa antigen genes were amplified. Phylogenetic analysis revealed that there were at least six definable clusters among the 68 isolates: 37% Karp-related strains (25/68), 27% TA763 strains (18/68), 12% JG-related strains (8/68), 19% Kato-related strains (13/68), 4% divergent strains (3/68), and 1% representing a Gilliam prototype strain (1/68). Overall, the O. tsutsugamushi genotypes exhibited a high degree of diversity, similar to that seen in strains from the rest of the areas where scrub typhus is endemic. Moreover, the 56-kDa protein sequence similarity between O. tsutsugamushi isolates from mites and those from human patients (H. Y. Lu et al., Am. J. Trop. Med. Hyg. 83:658-663, 2010) were striking, thus highlighting potential risk factors for this emerging zoonotic disease. 相似文献
1000.
Numerous studies have shown both the detrimental and beneficial effects of reactive oxygen species (ROS) in animals, plants, and fungi. These organisms utilize controlled generation of ROS for signaling, pathogenicity, and development. Here, we show that ROS are essential for the pathogenic development of Sclerotinia sclerotiorum, an economically important fungal pathogen with a broad host range. Based on the organism's completed genome sequence, we identified two S. sclerotiorum NADPH oxidases (SsNox1 and SsNox2), which presumably are involved in ROS generation. RNA interference (RNAi) was used to examine the function of SsNox1 and SsNox2. Silencing of SsNox1 expression indicated a central role for this enzyme in both virulence and pathogenic (sclerotial) development, while inactivation of the SsNox2 gene resulted in limited sclerotial development, but the organism remained fully pathogenic. ΔSsnox1 strains had reduced ROS levels, were unable to develop sclerotia, and unexpectedly correlated with significantly reduced oxalate production. These results are in accordance with previous observations indicating that fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of ROS regulation in the successful pathogenesis of S. sclerotiorum. 相似文献