全文获取类型
收费全文 | 988篇 |
免费 | 43篇 |
国内免费 | 1篇 |
专业分类
1032篇 |
出版年
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 17篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 17篇 |
2017年 | 16篇 |
2016年 | 20篇 |
2015年 | 35篇 |
2014年 | 22篇 |
2013年 | 82篇 |
2012年 | 75篇 |
2011年 | 69篇 |
2010年 | 40篇 |
2009年 | 39篇 |
2008年 | 60篇 |
2007年 | 44篇 |
2006年 | 60篇 |
2005年 | 49篇 |
2004年 | 62篇 |
2003年 | 34篇 |
2002年 | 59篇 |
2001年 | 5篇 |
2000年 | 9篇 |
1999年 | 5篇 |
1998年 | 11篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1995年 | 7篇 |
1994年 | 12篇 |
1993年 | 10篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1970年 | 3篇 |
1968年 | 4篇 |
排序方式: 共有1032条查询结果,搜索用时 0 毫秒
61.
Koji Morita Chikako Hasegawa Masakatsu Kaneko Shinya Tsutsumi Junko Sone Tomio Ishikawa Takeshi Imanishi Makoto Koizumi 《Bioorganic & medicinal chemistry letters》2002,12(1):73-76
To develop antisense oligonucleotides, novel nucleosides, 2'-O,4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks. The 1H NMR analysis showed that the 2'-O,4'-C-ethylene linkage of these nucleosides restricts the sugar puckering to the N-conformation as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA). The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (DeltaT(m)=+5.2 degrees C/modification) and were more nuclease-resistant than natural DNA and BNA/LNA. These results indicate that ENA have better properties as antisense oligonucleotides than BNA/LNA. 相似文献
62.
Horikawa Y Morohashi T Sano T Sakai N Yamada S Sasa R 《Biological trace element research》2006,112(3):263-271
We examine the effects of fructooligosaccharides (FOS) on the reduction in the incisor iron content in gastrectomized rat.
Twenty-eight 5-wk-old male Sprague-Dawley rats were divided into two groups: sham operated (bSH) and gastrectomized (bGX).
After 4 wk each group was divided into two subgroups according to the presence or absence of 7.5% FOS in the synthetic diet
(SH, SH+FOS, GX, and GX+FOS). At 10 wk wafter surgery, the maxilla was prepared to examine the iron content of the incisor
enamel surface at four points. These points corresponded to the iron content at 6,7,8, and 10 wk, respectively. Blood was
collected to determine serum iron levels at 4 and 10 wk. The serum iron level significantly decreased at 4 and 10 wk the GX
group. At 10 wk, the level in the GX+FOS group significantly increased but did not reaach that in the SH group. The iron content
of the enamel surface time-dependently increased and no significant differences were seen between SH and GX+FOS at 8 and 10
wk. These results suggest that FOS consumption impaired the loss of enamel content following gastrectomy, and this effect
preceded the effect on the serum iron level. 相似文献
63.
64.
Ogino Y Ohtake N Kobayashi K Kimura T Fujikawa T Hasegawa T Noguchi K Mase T 《Bioorganic & medicinal chemistry letters》2003,13(13):2167-2172
Optimization of the amine part of our original muscarinic M(3) receptor antagonist 1 was performed to identify M(3) receptor antagonists that are superior to 1. Compounds carrying a variety of diamine moieties without hydrophobic substituent on the nitrogen atom were screened against the binding affinity for the M(3) receptor and the selectivity for M(3) over the M(1) and M(2) receptors. This process led to a 4-aminopiperidinamide (2l) with a K(i) value of 5.1 nM and with a selectivity of the M(3) receptor that was 46-fold greater than that of the M(2) receptor. Further derivatization of 2l by inserting a spacer group or by incorporating alkyl group(s) into the amine part resulted in the identification of an 4-(aminoethyl)piperidinamide 2l-b with a K(i) value of 3.7 nM for the M(3) receptor and a selectivity for the M(3) receptor that was 170-fold greater than that of the M(2) receptor. 相似文献
65.
GM1 epitope tetrasaccharide was synthesized by a condensation of sialyl-alpha(2-3)-gal acceptor and gal-beta(1-3)-GalN donor in a highly efficient manner. After introduction of mercaptohexanol to the tetrasaccharide, it was coupled to maleimide-activated KLH carrier protein to give the desired GM1 epitope-KLH conjugate. 相似文献
66.
To determine whether lipid-secreting cells have cytosolic Ca2+ concentration ([Ca2+]c)-related secretory mechanisms, morphological changes and intracellular calcium dynamics of Harderian glands of guinea pigs stimulated by secretagogs were studied by electron microspy and Fura-2/AM digital image analysis. Control glandular cells contained large lipid vacuoles that were bordered by multi-layered membranes. Rough-surfaced endoplasmic reticulum, mitochondria, and smooth-surfaced endoplasmic reticulum may be involved in lipid vacuole formation. Myoepithelial cells surrounded alveoli. After carbamylcholine (CCh, 10–6, 10–5, and 10–3 M) stimulation, lipid materials within the membranous structures were frequently discharged by an exocytotic mechanism. Conspicuous deformation of glandular cells caused by vigorous contraction of myoepithelial cells was observed in isolated alveoli after 10–6M CCh stimulation, whereas the deformaties of glandular tissues perfused via vessels were small even after 10–3M CCh stimulation. Connective tissue between glandular alveoli inhibited unbridled myoepithelial-cell contraction. Fura-2/AM digital imaging analysis revealed that CCh stimulation caused an increase in [Ca2+]c in isolated alveoli. The morphological reactions and changes in [Ca2+]c were prevented by atropine. When extracellular calcium ions were absent, enhanced extrusion of lipid vacuoles, myoepithelial-cell contraction, and a rise in [Ca2+]c after CCh stimulation were not observed. Nicotine and catecholamines had no effect on the secretion or on the dynamics of [Ca2+]c. It can be concluded that acetylcholine elicits exocytosis in glandular cells and contraction of the myoepithelial cells of Harderian glands, accompanied by an increase in [Ca2+]c. The dynamics of [Ca2+]c of the gland alveoli are mostly dependent on extracellular Ca2+. 相似文献
67.
Norio Kurihara Yuzuru Sanemitsu Tomio Kimura Masaharu Kobayashi Minoru Nakajima Yoshiyuki Tamura 《Bioscience, biotechnology, and biochemistry》2013,77(5):784-797
β-BTC(3, 4/5, 6),1) γ-BTC(3, 4, 6/5), and ε-BTC(3, 4, 5/6) were synthesized from α-BTC (3, 6/4, 5) by stepwise routes. 相似文献
68.
69.
Engineering of Polyploid Saccharomyces cerevisiae for Secretion of Large Amounts of Fungal Glucoamylase 下载免费PDF全文
Keisuke Ekino Hiroyuki Hayashi Masahiro Moriyama Minoru Matsuda Masatoshi Goto Sadazo Yoshino Kensuke Furukawa 《Applied microbiology》2002,68(11):5693-5697
We engineered Saccharomyces cerevisiae cells that produce large amounts of fungal glucoamylase (GAI) from Aspergillus awamori var. kawachi. To do this, we used the δ-sequence-mediated integration vector system and the heat-induced endomitotic diploidization method. δ-Sequence-mediated integration is known to occur mainly in a particular chromosome, and the copy number of the integration is variable. In order to construct transformants carrying the GAI gene on several chromosomes, haploid cells carrying the GAI gene on different chromosomes were crossed with each other. The cells were then allowed to form spores, which was followed by dissection. Haploid cells containing GAI genes on multiple chromosomes were obtained in this way. One such haploid cell contained the GAI gene on five chromosomes and exhibited the highest GAI activity (5.93 U/ml), which was about sixfold higher than the activity of a cell containing one gene on a single chromosome. Furthermore, we performed heat-induced endomitotic diploidization for haploid transformants to obtain polyploid mater cells carrying multiple GAI genes. The copy number of the GAI gene increased in proportion to the ploidy level, and larger amounts of GAI were secreted. 相似文献
70.
Jo Ishizawa Kensuke Kojima Teresa McQueen Vivian Ruvolo Dhruv Chachad Graciela M. Nogueras-Gonzalez Xuelin Huang William E. Pierceall E. J. Dettman Michael H. Cardone Sharon Shacham Marina Konopleva Michael Andreeff 《PloS one》2015,10(9)
BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing cells to BH3-mimicking peptides. We hypothesized that basal levels of prosurvival BCL-2 family proteins may modulate the predictive power of BH3 profiling and termed it mitochondrial profiling. We investigated the correlation between cell sensitivity to apoptogenic agents and mitochondrial profiling, using a panel of acute myeloid leukemias induced to undergo apoptosis by exposure to cytarabine, the BH3 mimetic ABT-199, the MDM2 inhibitor Nutlin-3a, or the CRM1 inhibitor KPT-330. We found that the apoptogenic efficacies of ABT-199 and cytarabine correlated well with BH3 profiling reflecting BCL2, but not BCL-XL or MCL-1 dependence. Baseline BCL-2 protein expression analysis increased the ability of BH3 profiling to predict resistance mediated by MCL-1. By utilizing engineered cells with overexpression or knockdown of BCL-2 family proteins, Ara-C was found to be independent, while ABT-199 was dependent on BCL-XL. BCL-2 and BCL-XL overexpression mediated resistance to KPT-330 which was not reflected in the BH3 profiling assay, or in baseline BCL-2 protein levels. In conclusion, mitochondrial profiling, the combination of BH3 profiling and prosurvival BCL-2 family protein analysis, represents an improved approach to predict efficacy of diverse agents in AML and may have utility in the design of more effective drug combinations. 相似文献