全文获取类型
收费全文 | 4887篇 |
免费 | 380篇 |
国内免费 | 3篇 |
出版年
2024年 | 3篇 |
2023年 | 20篇 |
2022年 | 48篇 |
2021年 | 84篇 |
2020年 | 69篇 |
2019年 | 91篇 |
2018年 | 135篇 |
2017年 | 116篇 |
2016年 | 191篇 |
2015年 | 291篇 |
2014年 | 329篇 |
2013年 | 320篇 |
2012年 | 431篇 |
2011年 | 423篇 |
2010年 | 291篇 |
2009年 | 260篇 |
2008年 | 320篇 |
2007年 | 306篇 |
2006年 | 264篇 |
2005年 | 257篇 |
2004年 | 256篇 |
2003年 | 243篇 |
2002年 | 211篇 |
2001年 | 43篇 |
2000年 | 33篇 |
1999年 | 36篇 |
1998年 | 28篇 |
1997年 | 27篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 11篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有5270条查询结果,搜索用时 37 毫秒
71.
Won-Heong Lee Jin-Woo Kim Eun-Hee Park Nam Soo Han Myoung-Dong Kim Jin-Ho Seo 《Applied microbiology and biotechnology》2013,97(4):1561-1569
Sufficient supply of NADPH is one of the most important factors affecting the productivity of biotransformation processes. In this study, construction of an efficient NADPH-regenerating system was attempted using direct phosphorylation of NADH by NADH kinase (Pos5p) from Saccharomyces cerevisiae for producing guanosine diphosphate (GDP)-l-fucose and ε-caprolactone in recombinant Escherichia coli. Expression of Pos5p in a fed-batch culture of recombinant E. coli producing GDP-l-fucose resulted in a maximum GDP-l-fucose concentration of 291.5 mg/l, which corresponded to a 51 % enhancement compared with the control strain. In a fed-batch Baeyer–Villiger (BV) oxidation of cyclohexanone using recombinant E. coli expressing Pos5p, a maximum ε-caprolactone concentration of 21.6 g/l was obtained, which corresponded to a 96 % enhancement compared with the control strain. Such an increase might be due to the enhanced availability of NADPH in recombinant E. coli expressing Pos5p. These results suggested that efficient regeneration of NADPH was possible by functional expression of Pos5p in recombinant E. coli, which can be applied to other NADPH-dependent biotransformation processes in E. coli. 相似文献
72.
73.
Jun Park Yong Hwa Jo Chang Hoon Cho Wonchae Choe Insug Kang Hyung Hwan Baik Kyung-Sik Yoon 《Biochemical and biophysical research communications》2013,430(1):429-435
DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-β-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence. 相似文献
74.
Nguyen The Tung To Dao Cuong Tran Manh Hung Jeong Hyung Lee Mi Hee Woo Jae Sue Choi Jaewang Kim Sung Ho Ryu Byung Sun Min 《Bioorganic & medicinal chemistry letters》2013,23(5):1428-1432
Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D2 (2), butyl lucidenate E2 (3) and butyl lucidenate Q (4) along with 11 known compounds (5–15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW 264.7 cells. Compounds 1, 3, 4, 9, 10 and 15 showed inhibitory potency with IC50 values of 7.4, 6.4, 4.3, 9.4, 9.2 and 4.5 μM, respectively. Compounds 1, 3 and 15 dose-dependently reduced the LPS-induced iNOS expressions. Preincubation of cell with 1, 3 and 15 significantly suppressed LPS-induced expression of COX-2 protein. 相似文献
75.
76.
Seong Rim Byeon Hyunjin Vincent Kim Mijin Jeon Young Gil Ahn Maeng Sup Kim Jae Yang Kong Hye Yun Kim Young Soo Kim Dong Jin Kim 《Bioorganic & medicinal chemistry letters》2013,23(11):3467-3469
Alzheimer’s disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-β. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F = 46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD50 >2000 mg/kg) and hERG channel inhibition (14% at 10 μM) results indicated safety of KMS80013. 相似文献
77.
Akira Sakurai Yukiharu Sato Keun Hyung Park Nobutaka Takahashi Naohiko Yanagishima Isao Banno 《Bioscience, biotechnology, and biochemistry》2013,77(6):1451-1453
The pullulanase gene (pul) of Klebsiella aerogenes was transferred in vivo to Escherichia coli by using RP4:: Mu cts. The pul gene was expressed in E. coli, although the level of pullulanase activity in E. coli was lower than that in K. aerogenes, and the Pul+ transconjugants were relatively unstable in an unselective medium. Production of pullulanase, which is used to make maltose from starch, was induced in E. coli by pullulan, waxy maize amylopectin, soluble starch and maltose. When the transconjugant cells of E. coli were grown with pullulan or maltose, most pullulanase was produced intracellularly, whereas K. aerogenes produced pullulanase extracellularly. Retransfer of the pulk gene from E. coli to K. aerogenes by conjugation resulted in an increase of the production of extracellular pullulanase. 相似文献
78.
Hyunji Lee Hyeon-Son Choi Yooheon Park Chang Won Ahn Sung Ug Jung Soo Hyun Park 《Bioscience, biotechnology, and biochemistry》2013,77(10):1703-1709
Deer bone extract has the potential to relieve the discomfort or the articular cartilaginous damage associated with osteoarthritic (OA) and may be useful as a natural supplement for OA treatment without serious side effects. We analyzed the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced OA rats. Increases in the levels of serum pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly inhibited by the administration of deer bone extract (p?<?0.05). Decreases in the expression of collagen type II (COL2) and tissue inhibitors of metalloproteinases (TIMPs) mRNAs in the cartilage were significantly inhibited by deer bone extract treatment (p?<?0.05). The deer bone extract significantly suppressed the expression of matrix metalloproteinases (MMPs) mRNAs in the cartilage. The deer bone extract induced the up-regulation of COL2 and TIMP mRNAs and the down-regulation of MMP mRNAs by suppressing the expression of pro-inflammatory cytokine mRNAs. 相似文献
79.
Seongho Jang Eu Ddeum Park Hyung Joo Suh Sang Hun Lee Jin Soo Kim 《Bioscience, biotechnology, and biochemistry》2013,77(10):1716-1722
To investigate the activity of fermented deer antler on exercise endurance capacity, we evaluated endurance capacity in five-week-old male BALB/c mice by administering the fermented deer antler extract (FA) or the non-fermented deer antler extract (NFA) and then subjected the mice to exercise in the form of swimming. The mice administered 500?mg/kg/day of FA showed a significant increase in swimming time compared with mice administered placebo (16.55?min vs. 21.64?min, P?<?0.05). Serum lactate dehydrogenase (LDH), the marker of the liver and muscle damage, was significantly lower in FA groups. However, NFA groups did not show significantly different swimming time or serum LDH from that of the control group. Moreover, the FA-500 group had significantly higher hepatic superoxide dismutase (SOD) activity after forced swimming than the control and NFA groups (P?<?0.05). These findings suggest that fermentation may increase the exercise endurance capacity of the deer antler. 相似文献
80.
Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes into the site of inflammation. In this study, we investigated the inhibitory effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its underlying action mechanism in the TNF-α-stimulated keratinocytes. Curcumin induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent manners in the HaCaT cells. Curcumin suppressed TNF-α- induced ICAM-1 expression and subsequent monocyte adhesion, which were reversed by the addition of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory effect of curcumin on the TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that curcumin may exert its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes. [BMB Reports 2013;46(8): 410-415] 相似文献