全文获取类型
收费全文 | 1449篇 |
免费 | 69篇 |
国内免费 | 2篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 18篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 13篇 |
2017年 | 11篇 |
2016年 | 21篇 |
2015年 | 57篇 |
2014年 | 67篇 |
2013年 | 82篇 |
2012年 | 89篇 |
2011年 | 115篇 |
2010年 | 69篇 |
2009年 | 68篇 |
2008年 | 94篇 |
2007年 | 106篇 |
2006年 | 105篇 |
2005年 | 95篇 |
2004年 | 94篇 |
2003年 | 81篇 |
2002年 | 95篇 |
2001年 | 12篇 |
2000年 | 15篇 |
1999年 | 20篇 |
1998年 | 26篇 |
1997年 | 17篇 |
1996年 | 18篇 |
1995年 | 20篇 |
1994年 | 8篇 |
1993年 | 11篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 4篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有1520条查询结果,搜索用时 15 毫秒
71.
Downes M Verdecia MA Roecker AJ Hughes R Hogenesch JB Kast-Woelbern HR Bowman ME Ferrer JL Anisfeld AM Edwards PA Rosenfeld JM Alvarez JG Noel JP Nicolaou KC Evans RM 《Molecular cell》2003,11(4):1079-1092
The farnesoid X receptor (FXR) functions as a bile acid (BA) sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. However, BAs are poor reagents for characterizing FXR functions due to multiple receptor independent properties. Accordingly, using combinatorial chemistry we evolved a small molecule agonist termed fexaramine with 100-fold increased affinity relative to natural compounds. Gene-profiling experiments conducted in hepatocytes with FXR-specific fexaramine versus the primary BA chenodeoxycholic acid (CDCA) produced remarkably distinct genomic targets. Highly diffracting cocrystals (1.78 A) of fexaramine bound to the ligand binding domain of FXR revealed the agonist sequestered in a 726 A(3) hydrophobic cavity and suggest a mechanistic basis for the initial step in the BA signaling pathway. The discovery of fexaramine will allow us to unravel the FXR genetic network from the BA network and selectively manipulate components of the cholesterol pathway that may be useful in treating cholesterol-related human diseases. 相似文献
72.
A new primer pair (delta12-delta21) for polymerase chain reaction-based yeast typing was designed using the yeast genome sequence. The specificity of this primer pair was checked by the comparison of the electrophoresis pattern with a virtual profile calculated from Blast data. The analysis of 53 commercial and laboratory Saccharomyces cerevisiae yeast strains showed a clear improvement of interdelta analysis using the newly designed primers. 相似文献
73.
74.
Total lipid fatty acid composition was investigated in brain hemispheres of male Spontaneously Hypertensive Rats (SHR), compared with normotensive Wistar Kyoto rats (WKY) used as controls. Both strains were suckled by adoptive Wistar mothers, and then fed a standard diet after weaning. No difference was observed between the two hemispheres of WKY killed either at 10 or 30 days. In SHR killed at 10 days, the two hemispheres showed differences, SHR left hemispheres exhibiting greater fatty acid composition changes than those of WKY, phenomenon that toned down at 30 days. Hence, SHR pups showed a different total lipid fatty acid composition of their brain hemispheres when compared with their WKY controls, though the two strains received the same diet. Genetically programmed hypertension might be, directly or not, involved in these changes. 相似文献
75.
The 5' untranslated region and Gag product of Idefix, a long terminal repeat-retrotransposon from Drosophila melanogaster, act together to initiate a switch between translated and untranslated states of the genomic mRNA
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Meignin C Bailly JL Arnaud F Dastugue B Vaury C 《Molecular and cellular biology》2003,23(22):8246-8254
76.
In growing need of obtaining highly specific monoclonal antibodies against novel proteins, we developed new functions implemented in the program BEPITOPE to predict continuous protein epitopes. This program not only can compute, combine, display and print prediction profiles, but also provides a list of suggested linear peptides to be synthesized. Novel facilities incorporated in BEPITOPE include the treatment of a whole genome, the search for a user-defined pattern, and the combination of prediction to pattern profiles. This latter approach is useful to remove unwanted predictions such as those including glycosylation sites. 相似文献
77.
Hubschwerlen C Specklin JL Baeschlin DK Borer Y Haefeli S Sigwalt C Schroeder S Locher HH 《Bioorganic & medicinal chemistry letters》2003,13(23):4229-4233
Oxazolidinone-quinolone hybrids, which combine the pharmacophores of a quinolone and an oxazolidinone, were synthesised and shown to be active against a variety of susceptible and resistant Gram-positive and Gram-negative bacteria. The nature of the spacer greatly influences the antibacterial activity by directing the mode of action, that is quinolone- and/or oxazolidinone-like activity. The best compounds in this series have a balanced dual mode of action and overcome all types of resistance, including resistance to quinolones and linezolid, in clinically relevant Gram-positive pathogens. 相似文献
78.
The organophosphorous pesticide, demeton-S-methyl was transformed byCorynebacterium glutamicum in co-metabolism with more readilydegradable substrates. Glucose, acetate and fructose were tested as growth substrates, and the highest demeton-S-methyl biotransformation average rate (0.78 mg l-1 h-1) and maximum instantaneous rate (1.4 mg l-1 h-1) were achieved on fructose. This higher efficiency seems to be linked to the atypical behavior of C. glutamicum grown on fructose, characterized by a prolonged period of accelerating growth instead of a constant growth rate observed on glucose or acetate. More precisely, for growth rates in the 0.1–0.4 h-1 range, a direct coupling between the specific demeton-S-methyl consumption rate and the growth rate was demonstrated on fructose during batch –, steady state continuous – or continuous cultures with a controlled transient growth rate (accelerostat technology). The demeton-S-methyl biotransformation was more favoured during an acceleration phase of the growth rate. 相似文献
79.
Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector 总被引:21,自引:0,他引:21
Tamura T Thibert C Royer C Kanda T Abraham E Kamba M Komoto N Thomas JL Mauchamp B Chavancy G Shirk P Fraser M Prudhomme JC Couble P Toshiki T Chantal T Corinne R Toshio K Eappen A Mari K Natuo K Jean-Luc T Bernard M Gérard C Paul S Malcolm F Jean-Claude P Pierre C 《Nature biotechnology》2000,18(1):81-84
We have developed a system for stable germline transformation in the silkworm Bombyx mori L. using piggyBac, a transposon discovered in the lepidopteran Trichoplusia ni. The transformation constructs consist of the piggyBac inverted terminal repeats flanking a fusion of the B. mori cytoplasmic actin gene BmA3 promoter and the green fluorescent protein (GFP). A nonautonomous helper plasmid encodes the piggyBac transposase. The reporter gene construct was coinjected into preblastoderm eggs of two strains of B. mori. Approximately 2% of the individuals in the G1 broods expressed GFP. DNA analyses of GFP-positive G1 silkworms revealed that multiple independent insertions occurred frequently. The transgene was stably transferred to the next generation through normal Mendelian inheritance. The presence of the inverted terminal repeats of piggyBac and the characteristic TTAA sequence at the borders of all the analyzed inserts confirmed that transformation resulted from precise transposition events. This efficient method of stable gene transfer in a lepidopteran insect opens the way for promising basic research and biotechnological applications. 相似文献
80.
Langley Brett Vilotte Jean-Luc Stinnakre Marie-Georges Whitelaw C. Bruce A. L'Huillier Phil J. 《Transgenic research》1998,7(3):205-212
In an attempt to enhance the frequency and level of expression of a poor-performing MMTV-driven transgene, we co-integrated this construct with the ovine -lactoglobulin (BLG) gene in transgenic mice. Seven lines of transgenic mice possessing co-integrated BLG and MMTV-RZ5 transgenes were compared with 12 lines of mice that possessed only the MMTV-RZ5 construct. Co-integration enhanced the frequency of expression in the mammary gland from two out of 12 lines for the MMTV-RZ5 transgene alone, to five out of seven when co-integrated with BLG. Surprisingly, co-integration also resulted in co-expression of the two transgenes in the salivary gland, lung and spleen in addition to the mammary gland. Furthermore, both transgenes were expressed in virgin animals, and throughout pregnancy and lactation, suggesting that the developmental regulation of the locus follows that of the MMTV-promoter. These findings represent a novel locus control property of the ovine BLG gene that confer s commitment of the locus to the mammary gland, but also to a range of heterogeneous tissues possibly defined by the second promoter at the locus 相似文献