全文获取类型
收费全文 | 4041篇 |
免费 | 367篇 |
国内免费 | 448篇 |
专业分类
4856篇 |
出版年
2024年 | 12篇 |
2023年 | 113篇 |
2022年 | 77篇 |
2021年 | 100篇 |
2020年 | 172篇 |
2019年 | 149篇 |
2018年 | 139篇 |
2017年 | 169篇 |
2016年 | 167篇 |
2015年 | 144篇 |
2014年 | 178篇 |
2013年 | 252篇 |
2012年 | 159篇 |
2011年 | 183篇 |
2010年 | 170篇 |
2009年 | 220篇 |
2008年 | 223篇 |
2007年 | 243篇 |
2006年 | 180篇 |
2005年 | 154篇 |
2004年 | 173篇 |
2003年 | 130篇 |
2002年 | 111篇 |
2001年 | 123篇 |
2000年 | 117篇 |
1999年 | 107篇 |
1998年 | 69篇 |
1997年 | 72篇 |
1996年 | 74篇 |
1995年 | 46篇 |
1994年 | 63篇 |
1993年 | 44篇 |
1992年 | 45篇 |
1991年 | 54篇 |
1990年 | 44篇 |
1989年 | 37篇 |
1988年 | 28篇 |
1987年 | 39篇 |
1986年 | 29篇 |
1985年 | 31篇 |
1984年 | 34篇 |
1983年 | 26篇 |
1982年 | 26篇 |
1981年 | 20篇 |
1980年 | 27篇 |
1979年 | 19篇 |
1978年 | 15篇 |
1977年 | 9篇 |
1973年 | 12篇 |
1971年 | 9篇 |
排序方式: 共有4856条查询结果,搜索用时 0 毫秒
81.
Zhang R Mayhood T Lipari P Wang Y Durkin J Syto R Gesell J McNemar C Windsor W 《Analytical biochemistry》2004,331(1):138-146
MDM2 is an important negative regulator of the tumor suppressor protein p53 which regulates the expression of many genes including MDM2. The delicate balance of this autoregulatory loop is crucial for the maintenance of the genome and control of the cell cycle and apoptosis. MDM2 hyperactivity, due to amplification/overexpression or mutational inactivation of the ARF locus, inhibits the function of wild-type p53 and can lead to the development of a wide variety of cancers. Thus, the development of anti-MDM2 therapies may restore normal p53 function in tumor cells and induce growth suppression and apoptosis. We report here a novel high-throughput fluorescence polarization binding assay and its application in rank ordering small-molecule inhibitors that block the binding of MDM2 to a p53-derived fluorescent peptide. 相似文献
82.
83.
镉和锌在皖景天细胞内的分布及化学形态 总被引:11,自引:0,他引:11
运用差速离心法和化学试剂逐步提取法,分析了Cd和Zn在皖景天根、茎和叶的亚细胞分布及其化学形态.结果表明:10 μmol·L-1 Cd处理下,Cd在皖景天细胞内的主要分布位点是其可溶部分;在100 μmol·L-1 Cd处理下,Cd在根中主要分布在细胞壁、茎中主要分布在细胞壁和可溶部分、叶中超过90%的Cd分布在可溶部分.高Cd浓度处理时,皖景天根、茎和叶的细胞壁中Cd分布比例增加,而可溶部分Cd分布比例相对减少.在1和800 μmol·L-1 Zn处理条件下,Zn在皖景天根、茎和叶的主要分布位点是可溶部分;高Zn浓度处理时,皖景天叶、茎和根的可溶部分和细胞壁中Zn的分布比例无明显变化.细胞器中Zn和Cd分布都很少.Cd在皖景天根、茎和叶内主要以氯化钠提取态和水提取态存在,Zn在皖景天根、茎和叶内以多种化学形态存在. 相似文献
84.
Respiratory complex I couples the transfer of electrons from NADH to ubiquinone and the translocation of protons across the mitochondrial membrane. A detailed understanding of the midpoint reduction potentials (Em) of each redox center and the factors which influence those potentials are critical in the elucidation of the mechanism of electron transfer in this enzyme. We present accurate electrostatic interaction energies for the iron-sulfur (FeS) clusters of complex I to facilitate the development of models and the interpretation of experiments in connection to electron transfer (ET) in this enzyme. To calculate redox titration curves for the FeS clusters it is necessary to include interactions between clusters, which in turn can be used to refine Em values and validate spectroscopic assignments of each cluster. Calculated titration curves for clusters N4, N5, and N6a are discussed. Furthermore, we present some initial findings on the electrostatics of the redox centers of complex I under the influence of externally applied membrane potentials. A means of determining the location of the FeS cofactors within the holo-complex based on electrostatic arguments is proposed. A simple electrostatic model of the protein/membrane system is examined to illustrate the viability of our hypothesis. 相似文献
85.
Correlated binary regression using a quadratic exponential model 总被引:5,自引:0,他引:5
86.
Three models were constructed for analyzing the population characteristics ofC. chinensis on stored beans; model A describing the whole reproductive process with a single equation, model B describing the three age-specific processes (oviposition, egg survival and larval survival) with separate equations, and model C which describes all these processes not for the whole habitat but for the individual beans comprizing it. The logit equation was employed here as a common basis to describe the density-response relationship involved. All three models showed very good fit to the experimental data obtained for both laboratory and wild strains of the weevil. The parameter values characterizing the population dynamics were, however, widely different between the two strains; the laboratory one which had been reared for some 500 generations showed significantly higher reproductive capacity, less sensitive and gentler response to crowding in both adult and egg stages, and more uniform egg distribution among individual beans, as compared with the wild strain newly introduced. Sensitivity analyses using these models suggested that these changes in population characteristics have been attained by the process of domestication or adaptation to stable laboratory conditions through a long period of time. This process seemed in effect to have optimized the population's performances in the laboratory environment. Evolutionary significance of such optimization was discussed with reference to the selection pressure which may have acted upon individuals. 相似文献
87.
David L. Remington P?ivi H. Leinonen Johanna Lepp?l? Outi Savolainen 《Genetics》2013,195(3):1087-1102
Costs of reproduction due to resource allocation trade-offs have long been recognized as key forces in life history evolution, but little is known about their functional or genetic basis. Arabidopsis lyrata, a perennial relative of the annual model plant A. thaliana with a wide climatic distribution, has populations that are strongly diverged in resource allocation. In this study, we evaluated the genetic and functional basis for variation in resource allocation in a reciprocal transplant experiment, using four A. lyrata populations and F2 progeny from a cross between North Carolina (NC) and Norway parents, which had the most divergent resource allocation patterns. Local alleles at quantitative trait loci (QTL) at a North Carolina field site increased reproductive output while reducing vegetative growth. These QTL had little overlap with flowering date QTL. Structural equation models incorporating QTL genotypes and traits indicated that resource allocation differences result primarily from QTL effects on early vegetative growth patterns, with cascading effects on later vegetative and reproductive development. At a Norway field site, North Carolina alleles at some of the same QTL regions reduced survival and reproductive output components, but these effects were not associated with resource allocation trade-offs in the Norway environment. Our results indicate that resource allocation in perennial plants may involve important adaptive mechanisms largely independent of flowering time. Moreover, the contributions of resource allocation QTL to local adaptation appear to result from their effects on developmental timing and its interaction with environmental constraints, and not from simple models of reproductive costs. 相似文献
88.
Keigo Gohda 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):609-615
In this study, we investigated by linear regression model the SAR data of the 15 HIV-1 protease inhibitors possessing structurally diverse scaffolds. First, a regression model was developed only using the enzyme-inhibitor interaction energy as a term of the model, but did not provide a good correlation with the inhibitory activity (R2 = 0.580 and Q2 = 0.500). Then, we focused on the conformational flexibility of the inhibitors which may represent the diversity of the inhibitors, and added two conformational parameters into the model, respectively: the number of rotatable bonds of ligands (ΔSrot) and the distortion energy of ligands (ΔElig). The regression model by adding ΔElig successfully improved the quality of the model (R2 = 0.771 and Q2 = 0.713) while the model with ΔSrot was unsuccessful. The prediction for a training inhibitor by the ΔElig model also showed good agreement with experimental activity. These results suggest that the conformational flexibility of HIV-1 protease inhibitors directly contributes to the enzyme inhibition. 相似文献
89.
90.