全文获取类型
收费全文 | 6628篇 |
免费 | 307篇 |
国内免费 | 277篇 |
专业分类
7212篇 |
出版年
2024年 | 11篇 |
2023年 | 77篇 |
2022年 | 150篇 |
2021年 | 159篇 |
2020年 | 220篇 |
2019年 | 313篇 |
2018年 | 315篇 |
2017年 | 205篇 |
2016年 | 207篇 |
2015年 | 170篇 |
2014年 | 423篇 |
2013年 | 669篇 |
2012年 | 196篇 |
2011年 | 406篇 |
2010年 | 224篇 |
2009年 | 282篇 |
2008年 | 288篇 |
2007年 | 313篇 |
2006年 | 259篇 |
2005年 | 271篇 |
2004年 | 241篇 |
2003年 | 216篇 |
2002年 | 182篇 |
2001年 | 109篇 |
2000年 | 84篇 |
1999年 | 90篇 |
1998年 | 83篇 |
1997年 | 103篇 |
1996年 | 109篇 |
1995年 | 81篇 |
1994年 | 62篇 |
1993年 | 70篇 |
1992年 | 62篇 |
1991年 | 52篇 |
1990年 | 29篇 |
1989年 | 42篇 |
1988年 | 25篇 |
1987年 | 34篇 |
1986年 | 29篇 |
1985年 | 31篇 |
1984年 | 70篇 |
1983年 | 41篇 |
1982年 | 51篇 |
1981年 | 31篇 |
1980年 | 31篇 |
1979年 | 31篇 |
1978年 | 11篇 |
1977年 | 17篇 |
1976年 | 12篇 |
1974年 | 14篇 |
排序方式: 共有7212条查询结果,搜索用时 9 毫秒
71.
Sultan Ullah Yujin Park Muhammad Ikram Sanggwon Lee Chaeun Park Dongwan Kang Jungho Yang Jinia Akter Sik Yoon Pusoon Chun Hyung Ryong Moon 《Bioorganic & medicinal chemistry》2018,26(21):5672-5681
Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25?µM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-β-phenyl-α,β-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents. 相似文献
72.
Boggiano C Jiang S Lu H Zhao Q Liu S Binley J Blondelle SE 《Biochemical and biophysical research communications》2006,347(4):909-915
Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide dC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While dC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1alpha to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of dC13 implies additional mode(s) of action. These results suggest that dC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors. 相似文献
73.
74.
Bishop JG 《Molecular biology and evolution》2005,22(7):1531-1534
Polygalacturonase inhibitor proteins (PGIPs) protect plants against invasion by diverse microbial and invertebrate enemies that use polygalacturonase (PG) to breach the plant cell wall. Directed mutagenesis has identified specific natural mutations conferring novel defensive capability in green bean PGIP against a specific fungal PG. These same sites are identified as positively selected by phylogenetic codon-substitution models, demonstrating the utility of such models for connecting retrospective comparative analyses with contemporary, ecologically relevant variation. 相似文献
75.
Richard B. Silverman Graham R. Lawton Hantamalala Ralay Ranaivo Laura K. Chico Jiwon Seo D. Martin Watterson 《Bioorganic & medicinal chemistry》2009,17(21):7593-7605
Several prodrug approaches were taken to mask amino groups in two potent and selective neuronal nitric oxide synthase (nNOS) inhibitors containing either a primary or secondary amino group to lower the charge and improve blood–brain barrier (BBB) penetration. The primary amine was masked as an azide and the secondary amine as an amide or carbamate. The azide was not reduced to the amine under a variety of in vitro and ex vivo conditions. Despite the decrease in charge of the amino group as an amide and as carbamates, BBB penetration did not increase. It appears that the uses of azides as prodrugs for primary amines or amides and carbamates as prodrugs for secondary amines are not universally effective for CNS applications. 相似文献
76.
Yakai Xin Yu Guo Yanle Li Yujin Ma Liping Li Hongwei Jiang 《Saudi Journal of Biological Sciences》2019,26(2):421-426
To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, and CENTRAL were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to Aug 10, 2017, without language or date restrictions. Thirty-one studies totaling 13,650 patients were included. SGLT2 inhibitors significantly decreased SUA levels compared with placebo, canagliflozin WMD –37.02?μmol/L, 95% CI [–38.41, –35.63], dapagliflozin WMD –38.05?μmol/L, 95% CI [–44.47, –31.62], empagliflozin WMD –42.07?μmol/L, 95% CI [–46.27, –37.86]. The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia. 相似文献
77.
野鸦椿种子内源抑制物活性初探 总被引:2,自引:0,他引:2
以野鸦椿(Euscaphis japonica)种壳和胚为材料,甲醇浸提得到种壳浸提液和胚浸提液,配制浸提液浓度梯度为原浸提液浓度的10%、20%、30%、40%,研究不同浓度的种壳和胚浸提液对白菜、小麦、绿豆种子底物酶活性、发芽率、幼苗根长和苗高的影响,萃取和分离种壳和胚甲醇浸提液中的内源抑制物质,探讨野鸦椿种子内源抑制物质的活性与成分。结果表明:随着种壳和胚浸提液浓度的增加,白菜种子酸性磷酸酶活性和发芽率均显著降低(P0.05),表现为抑制作用递增,种壳的抑制作用小于胚,而幼苗的根长和苗高则表现为低促高抑,在10%浸提液处理下根长和苗高达最大值,种壳的促进效果弱于胚;小麦种子淀粉酶活性及幼苗的根长和苗高递减(P0.05),表现为抑制作用递增,而发芽率则在浓度≤20%时差异不明显(P0.05),浓度为30%时显著降低(P0.05),40%时发芽率为0,种壳的抑制作用大于胚;绿豆种子蛋白酶活性、发芽率、幼苗根长和苗高均在浸提液浓度≥20%时显著下降(P0.05),且种壳的作用效果小于胚。种子内源抑制物萃取及分离表明,外壳中含酚酸类较胚多,含碱类较胚少。综上认为,野鸦椿种壳和胚中均含有较高活性的内源抑制物,但性质、成分及含量存在差异,外壳内源抑制物主要作用对象为淀粉类物质,胚乳内源抑制物主要作用于油脂类和蛋白类物质。 相似文献
78.
Darja Barlič Maganja Borut Štrukelj Jože Pungerčar Franc Gubenšek Vito Turk Igor Kregar 《Plant molecular biology》1992,20(2):311-313
A genomic DNA clone encoding an aspartic proteinase inhibitor of potato was isolated from a lambda EMBL3 phage library using the aspartic proteinase inhibitor cDNA as a hybridization probe. The gene has all characteristic sequences normally found in eucaryotic genes. Typical CAAT and TATA box sequences were found in the 5-upstream region. In this part are also two putative regulatory AGGA box sequences located. In the genomic sequence there are no intron sequences interrupting the coding region. An open reading frame of the gene encodes a precursor protein of 217 amino acids which shows high percent identity with the aspartic proteinase inhibitor cDNA. 相似文献
79.
Alejandra Rubio María V. Cardo Melania T. Junges Aníbal E. Carbajo Darío Vezzani 《Journal of Asia》2018,21(1):150-155
Aedes aegypti and Culex pipiens s.l. (Linnaeus, 1762 and 1758, respectively) (Diptera: Culicidae) are important vectors of diseases to humans and a growing public health concern. In order to contribute to the control of mosquito vectors by low environmental impact approaches we assessed the susceptibility of natural populations of container-breeding mosquitoes to triflumuron, an insect growth regulator, in temperate Argentina. A field trial was conducted to evaluate the efficacy of two doses (0.5 ppm and 1 ppm) of triflumuron (SC 48%) against natural populations of Ae. aegypti and Culex spp. immatures in flower vases of four cemeteries. The results demonstrated the susceptibility of both target mosquitoes to triflumuron in field conditions. For Ae. aegypti, dose-dependent reductions were achieved in the presence of pupae and the percentage of water-holding containers harbouring L3–4 and/or pupae, whereas the larvae abundance was equally reduced for both doses. For Culex spp., similar levels of reduction of larvae abundance and pupae presence were achieved with both doses. Significant effects on the response variables measured were recorded up to six to eight weeks post-intervention. Bimonthly applying 1 ppm triflumuron in the context of an integrated mosquito management should achieve a lasting control of Ae. aegypti and Culex spp. in small artificial containers with minimal environmental impacts. 相似文献
80.