全文获取类型
收费全文 | 20433篇 |
免费 | 1782篇 |
国内免费 | 4篇 |
出版年
2023年 | 62篇 |
2022年 | 112篇 |
2021年 | 342篇 |
2020年 | 189篇 |
2019年 | 257篇 |
2018年 | 336篇 |
2017年 | 299篇 |
2016年 | 441篇 |
2015年 | 866篇 |
2014年 | 919篇 |
2013年 | 1154篇 |
2012年 | 1589篇 |
2011年 | 1574篇 |
2010年 | 929篇 |
2009年 | 931篇 |
2008年 | 1267篇 |
2007年 | 1295篇 |
2006年 | 1174篇 |
2005年 | 1185篇 |
2004年 | 1060篇 |
2003年 | 1000篇 |
2002年 | 993篇 |
2001年 | 250篇 |
2000年 | 203篇 |
1999年 | 245篇 |
1998年 | 301篇 |
1997年 | 189篇 |
1996年 | 171篇 |
1995年 | 162篇 |
1994年 | 147篇 |
1993年 | 133篇 |
1992年 | 144篇 |
1991年 | 130篇 |
1990年 | 130篇 |
1989年 | 131篇 |
1988年 | 107篇 |
1987年 | 94篇 |
1986年 | 103篇 |
1985年 | 101篇 |
1984年 | 126篇 |
1983年 | 108篇 |
1982年 | 107篇 |
1981年 | 124篇 |
1980年 | 107篇 |
1979年 | 82篇 |
1978年 | 85篇 |
1977年 | 73篇 |
1975年 | 65篇 |
1974年 | 82篇 |
1973年 | 60篇 |
排序方式: 共有10000条查询结果,搜索用时 406 毫秒
991.
Anwaruzzaman M Chin BL Li XP Lohr M Martinez DA Niyogi KK 《Photosynthesis research》2004,82(3):265-276
When the absorption of light energy exceeds the capacity for its utilization in photosynthesis, regulation of light harvesting is critical in order for photosynthetic organisms to minimize photo-oxidative damage. Thermal dissipation of excess absorbed light energy, measured as non-photochemical quenching (NPQ) of chlorophyll fluorescence, is induced rapidly in response to excess light conditions, and it is known that xanthophylls such as zeaxanthin and lutein, the transthylakoid pH gradient, and the PsbS protein are involved in this mechanism. Although mutants affecting NPQ and the biosynthesis of zeaxanthin and lutein were originally isolated and characterized at the physiological level in the unicellular green alga Chlamydomonas reinhardtii, the molecular basis of several of these mutants, such as npq1 and lor1, has not been determined previously. The recent sequencing of the C. reinhardtii nuclear genome has facilitated the search for C. reinhardtii homologs of plant genes involved in xanthophyll biosynthesis and regulation of light harvesting. Here we report the identification of C. reinhardtii genes encoding PsbS and lycopene ɛ-cyclase, and we show that the lor1 mutation, which affects lutein synthesis, is located within the lycopene ɛ-cyclase gene. In contrast, no homolog of the plant violaxanthin de-epoxidase (VDE) gene was found. Molecular markers were used to map the npq1 mutation, which affects VDE activity, as a first step toward the map-based cloning of the NPQ1 gene. 相似文献
992.
Tropical biodiversity continues to erode unabated, which calls for ecologists to address the problem directly, placing less reliance on indirect interventions, such as community-based development schemes. Ecologists must become more assertive in providing scientifically formulated and adaptively managed interventions, involving biodiversity payments, to serve local, regional and global interests in tropical nature. Priorities for tropical ecologists thus include the identification of key thresholds to ecological resilience, and the formulation of clear monitoring protocols and management strategies for implementation by local resource managers. A particular challenge is to demonstrate how nature reserves contribute to the adaptive capacity of regional land-use matrices and, hence, to the provision of sustainable benefits at multiple spatial and temporal scales. 相似文献
993.
A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins 总被引:34,自引:0,他引:34
The HIV-1 Vif protein suppresses the inhibition of viral replication caused by the human antiretroviral factor APOBEC3G. As a result, HIV-1 mutants that do not express the Vif protein are replication incompetent in 'nonpermissive' cells, such as primary T cells and the T-cell line CEM, that express APOBEC3G. In contrast, Vif-defective HIV-1 replicates effectively in 'permissive' cell lines, such as a derivative of CEM termed CEM-SS, that do not express APOBEC3G. Here, we show that a second human protein, APOBEC3F, is also specifically packaged into HIV-1 virions and inhibits their infectivity. APOBEC3F binds the HIV-1 Vif protein specifically and Vif suppresses both the inhibition of virus infectivity caused by APOBEC3F and virion incorporation of APOBEC3F. Surprisingly, APOBEC3F and APOBEC3G are extensively coexpressed in nonpermissive human cells, including primary lymphocytes and the cell line CEM, where they form heterodimers. In contrast, both genes are quiescent in the permissive CEM derivative CEM-SS. Together, these data argue that HIV-1 Vif has evolved to suppress at least two distinct but related human antiretroviral DNA-editing enzymes. 相似文献
994.
Stearns BA Anker N Arruda JM Campbell BT Chen C Cramer M Hu T Jiang X Park K Ren KK Sablad M Santini A Schaffhauser H Urban MO Munoz B 《Bioorganic & medicinal chemistry letters》2004,14(5):1295-1298
A novel class of 6-aryl-6H-pyrrolo[3,4-d]pyridazine ligands for the alpha2delta subunit of voltage-gated calcium channels has been described. Substitutions in the aryl ring of the molecule were generally not tolerated, and resulted in diminished binding to the alpha2delta subunit. Modifications to the pyridazine ring revealed numerous permissive substitutions, and detailed SAR studies were carried out in this portion of the molecule. Replacement of the pyridazine ring methyl group with an aminomethyl functionality provided greatly improved potency over the initial lead. The initial lead compound displayed good rat pharmacokinetic properties, and was shown to be efficacious in the Chung model for neuropathic pain in rats. 相似文献
995.
The development of potent non-peptidic PTP-1B inhibitors 总被引:2,自引:0,他引:2
Dufresne C Roy P Wang Z Asante-Appiah E Cromlish W Boie Y Forghani F Desmarais S Wang Q Skorey K Waddleton D Ramachandran C Kennedy BP Xu L Gordon R Chan CC Leblanc Y 《Bioorganic & medicinal chemistry letters》2004,14(4):1039-1042
The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM). 相似文献
996.
997.
Kim TS Hague AB Lee TI Lian B Tegley CM Wang X Burgess TL Qian YX Ross S Tagari P Lin CH Mayeda C Dao J Jordan S Mohr C Cheetham J Viswanadhan V Tasker AS 《Bioorganic & medicinal chemistry letters》2004,14(1):87-90
A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines were synthesized and tested against cathepsin K, cathepsin L and cathepsin B. These new non-covalent inhibitors exhibited single-digit nM inhibition of the cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and human osteoclast resorption assays. 相似文献
998.
Eastman B Chen C Smith ND Poon S Chung J Reyes-Manalo G Cosford ND Munoz B 《Bioorganic & medicinal chemistry letters》2004,14(22):5485-5488
The SAR of the lead compounds 2a and 2b was rapidly explored. Utilizing a parallel solution-phase Suzuki coupling approach, in tandem with strong cation exchange resin (SCX) purification afforded the desired focused library. The library was evaluated in vitro, a ninefold potency increase was achieved and the preference for ortho substitution of moderate steric bulk of the fourth, phenyl ring was identified. In addition, dimethylisoxazole, as a heterocyclic replacement for the phenylic ring of the lead compound, was also identified by this approach. 相似文献
999.
Gallagher BM Fang FG Johannes CW Pesant M Tremblay MR Zhao H Akasaka K Li XY Liu J Littlefield BA 《Bioorganic & medicinal chemistry letters》2004,14(3):575-579
Analogues of the marine natural product (-)-laulimalide were prepared by total synthesis and evaluated in vitro for anticancer activity. 相似文献
1000.
Li J DeMello KM Cheng H Sakya SM Bronk BS Rafka RJ Jaynes BH Ziegler CB Kilroy C Mann DW Nimz EL Lynch MP Haven ML Kolosko NL Minich ML Li C Dutra JK Rast B Crosson RM Morton BJ Kirk GW Callaghan KM Koss DA Shavnya A Lund LA Seibel SB Petras CF Silvia A 《Bioorganic & medicinal chemistry letters》2004,14(1):95-98
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted. 相似文献