全文获取类型
收费全文 | 699篇 |
免费 | 66篇 |
出版年
2021年 | 8篇 |
2020年 | 4篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 12篇 |
2014年 | 25篇 |
2013年 | 42篇 |
2012年 | 25篇 |
2011年 | 40篇 |
2010年 | 23篇 |
2009年 | 30篇 |
2008年 | 39篇 |
2007年 | 37篇 |
2006年 | 29篇 |
2005年 | 29篇 |
2004年 | 29篇 |
2003年 | 38篇 |
2002年 | 21篇 |
2001年 | 19篇 |
2000年 | 44篇 |
1999年 | 33篇 |
1998年 | 16篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 15篇 |
1994年 | 12篇 |
1993年 | 7篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 10篇 |
1989年 | 12篇 |
1988年 | 11篇 |
1987年 | 3篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 7篇 |
1970年 | 3篇 |
1969年 | 6篇 |
1968年 | 5篇 |
1966年 | 2篇 |
排序方式: 共有765条查询结果,搜索用时 15 毫秒
81.
Manabu Yamada Mitsuji Yamashita Takuya Suyama Junko Yamashita Kazuhide Asai Taishi Niimi Nobuhisa Ozaki Michio Fujie Kasthuraiah Maddali Satoki Nakamura Kazunori Ohnishi 《Bioorganic & medicinal chemistry letters》2010,20(19):5943-5946
4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (3c) was first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec®, which is known as a molecule targeting chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4 position with methyl groups as well as 4-bromo substituent suggests a good anti-proliferative effect. 相似文献
82.
Ibicella lutea and Proboscidea louisiana, both of the Martyniaceae family, are known for rich glandular trichomes on their leaves and stems. Chemical investigations of the glandular trichome exudates on leaves of the two plants furnished three types of secondary metabolites, glycosylated fatty acids, glycerides (2-O-(3,6-diacetyloxyfattyacyl)glycerols and 2-O-(3-acetyloxyfattyacyl)glycerols) and dammarane triterpenes. The glycosylated fatty acids from I. lutea were determined to be 6(S)-(6-O-acetyl-β-d-glucopyranosyloxy)-octadecanoic acid (1A), -eicosanoic acid (1B) and -docosanoic acid (1C), as well as their respective deacetyl congeners (2A, 2B and 2C), whereas P. louisiana furnished 8(S)-(6-O-acetyl-β-d-glucopyranosyloxy)-eicosanoic acid (3A) and -docosanoic acid (3B) and their respective deacetyl congeners (4A and 4B), together with 2B. Both plants contained 12 identical 2-O-[(3R,6S)-3,6-diacetyloxyfattyacyl]glycerols (5A-L), in which the fatty acyl moieties contained between 17 and 21 carbon atoms. The corresponding mono-acetyloxy compounds, 2-O-[(3R)-3-acetyloxyfattyacyl]glycerols (6A–L) were detected in both plants. Among these glycerides, ten compounds (5A, 5C, 5F, 5H, 5K, 6A, 6C, 6F, 6H and 6K) had iso-fattyacyl structures and four (5E, 5J, 6E and 6J) had anteiso-fattyacyl structures. A previously unknown dammarane triterpene, betulatriterpene C 3-acetate (7), was isolated together with three known dammarane triterpenes, 24-epi-polacandrin 1,3-diacetate (8), betulatriterpene C (9) and 24-epi-polacandrin 3-acetate (10) from I. lutea, whereas 12 dammarane triterpenes, named probosciderols A–L (12–23), and the known compound betulafolienetriol (11) were isolated from P. louisiana. The structures of these compounds were elucidated by spectroscopic analysis including 2D-NMR techniques and chemical transformations. The 6-O-acetylglucosyloxy-fatty acids 1A–C (42%) and the dammarane triterpenes 7–10 (31%) were the two most abundant constituents in the glandular trichome exudate of I. lutea, whereas the dammarane triterpenes 11–23 (47%) and the glucosyloxy-fatty acids (4A, 4B and 2B) (38%) were the most abundant constituents in the glandular trichome exudate of P. louisiana. 相似文献
83.
Asai Y Makimura Y Kawabata A Ogawa T 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(11):7674-7683
Soluble CD14 (sCD14) in serum is known to sensitize host cells to LPS. In the present study, the contributions of sCD14 and LPS-binding protein to a lipid A moiety from LPS preparations of periodontopathogenic Fusobacterium nucleatum sp. nucleatum were compared with that of Escherichia coli-type synthetic lipid A (compound 506). F. nucleatum lipid A was identified to be a hexa-acylated fatty acid composed of tetradecanoate (C(14)) and hexadecanoate (C(16)), similar to dodecanoate (C(12)) and C(14) in compound 506. The two lipid A specimens exhibited nearly the same reactivity in Limulus amoebocyte lysate assays, though F. nucleatum lipid A showed a weaker lethal toxicity. Both lipid A specimens showed nearly the same activities toward host cells in the absence of FBS, though compound 506 exhibited much stronger activity in the presence of FBS, sCD14, or sCD14 together with LPS-binding protein. Furthermore, native PAGE/Western immunoblot assays demonstrated that F. nucleatum lipid A had a weaker binding to sCD14 as compared with compound 506. These results suggest that sCD14 is able to discriminate the slight structural differences between these lipid As, which causes their distinct host cell activation activities. 相似文献
84.
85.
Sakakibara Y Popendorf K Ogawa N Asai K Sato K 《Journal of bioinformatics and computational biology》2007,5(5):1103-1122
Several computational methods based on stochastic context-free grammars have been developed for modeling and analyzing functional RNA sequences. These grammatical methods have succeeded in modeling typical secondary structures of RNA, and are used for structural alignment of RNA sequences. However, such stochastic models cannot sufficiently discriminate member sequences of an RNA family from nonmembers and hence detect noncoding RNA regions from genome sequences. A novel kernel function, stem kernel, for the discrimination and detection of functional RNA sequences using support vector machines (SVMs) is proposed. The stem kernel is a natural extension of the string kernel, specifically the all-subsequences kernel, and is tailored to measure the similarity of two RNA sequences from the viewpoint of secondary structures. The stem kernel examines all possible common base pairs and stem structures of arbitrary lengths, including pseudoknots between two RNA sequences, and calculates the inner product of common stem structure counts. An efficient algorithm is developed to calculate the stem kernels based on dynamic programming. The stem kernels are then applied to discriminate members of an RNA family from nonmembers using SVMs. The study indicates that the discrimination ability of the stem kernel is strong compared with conventional methods. Furthermore, the potential application of the stem kernel is demonstrated by the detection of remotely homologous RNA families in terms of secondary structures. This is because the string kernel is proven to work for the remote homology detection of protein sequences. These experimental results have convinced us to apply the stem kernel in order to find novel RNA families from genome sequences. 相似文献
86.
Highly polar xanthophylls of 9′-cis-neoxanthin (neoxanthin) and fucoxanthin, which have the characteristic structure of an epoxy group and an allenic bond, were
previously found to induce apoptosis in human prostate cancer cells. In the present study, we found apoptosis induction by
neoxanthin in HCT116 human colon cancer cells and examined the induction mechanism. The cells exposed to 20 μM neoxanthin
clearly showed chromatin condensation, DNA fragmentation, and an increase in hypodiploid cells. Neoxanthin treatment increased
the activities of caspase-3, -8 and -9, and the protein levels of their active subunits, except in the case of caspase-8.
The treatment also caused the loss of mitochondrial transmembrane potential at an early stage and subsequently the release
of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to cytosol. The exposure of neoxanthin directly to mitochondria
isolated from the cells enhanced the release of cytochrome c and AIF in a dose-dependent manner. Approximately 50% of the
neoxanthin taken up into the HCT116 cells accumulated in the mitochondrial fraction. These results suggest that the accumulation
of neoxanthin in mitochondria causes the loss of mitochondrial transmembrane potential and thereafter releases cytochrome
c and AIF, leading to the execution of apoptosis. 相似文献
87.
We examined how differently timed stimuli to one auditory cortex affect the spike trains they drive in the controlateral homotopic field of anesthetized rats. Bipolar electrical stimulations consisted of trains of pulses (100 micro s, <500 micro A) at rates of 25, 50 or 125 pulses/s and with different stimulus patterns (i.e., dispersions, sequences), called "pacemaker", "accelerando" or "decelerando". Trains lasted for 342 ms and were separated by 4 s. When trains were evaluated over times comparable to the stimulus duration changes characteristically involved an initial slowing followed by recovery and several discharges both stimulus- and neuron-dependent. When evaluated by cross-correlations between cortical cell pairs, the changes extended far beyond the stimulus end. Results suggest that interhemispheric projections, by way of their averages and patterns, play key, long duration roles in the spike-dependent properties of cortical synapses (e.g., potentiation, depression) and thus of cortical circuit operations. 相似文献
88.
Terauchi T Asai N Doko T Taguchi R Takenaka O Sakurai H Yonaga M Kimura T Kajiwara A Niidome T Kume T Akaike A Sugimoto H 《Bioorganic & medicinal chemistry》2007,15(22):7098-7107
We present efficient syntheses of serofendic acids A and B (SA-A and SA-B), novel neuroprotective substances isolated from fetal calf serum. Biological and pharmacological evaluation showed that SA-A and SA-B have potent protective action against glutamate-induced neurotoxicity, but do not interact directly with glutamate receptors. A pharmacokinetic study showed that they have good oral bioavailability in rats. The results indicate that SA-A and SA-B are potential lead compounds for candidate drugs to treat various neurological disorders. 相似文献
89.
The identification of novel miRNAs has significant biological and clinical importance. However, none of the known miRNA features alone is sufficient for accurately detecting novel miRNAs. The aim of this paper is to integrate these features in a straightforward manner for detecting miRNAs with better accuracy. Since most miRNA regions are highly conserved among vertebrates for the ability to form stable hairpin structures, we implemented a hidden Markov model that outputs multidimensional feature vectors composed of both evolutionary features and secondary structural ones. The proposed method, called miRRim, outperformed existing ones in terms of detection/prediction performance: The total number of predictions was smaller than with existing methods when the number of miRNAs detected was adjusted to be the same. Moreover, there were several candidates predicted only by our method that are clustered with the known miRNAs, suggesting that our method is able to detect novel miRNAs. Genomic coordinates of predicted miRNA can be obtained from http://mirrim.ncrna.org/. 相似文献
90.
Sakai M Hirata H Sayama H Sekiguchi K Itano H Asai T Dohra H Hara M Watanabe N 《Bioscience, biotechnology, and biochemistry》2007,71(10):2408-2419
We investigated the biosynthetic pathway for 2-phenylethanol, the dominant floral scent compound in roses, using enzyme assays. L-[(2)H8] Phenylalanine was converted to [(2)H8] phenylacetaldehyde and [(2)H8]-2-phenylethanol by two enzymes derived from the flower petals of R. 'Hoh-Jun,' these being identified as pyridoxal-5'-phosphate-dependent L-aromatic amino acid decarboxylase (AADC) and phenylacetaldehyde reductase (PAR). The activity of rose petal AADC to yield phenylacetaldehyde was nine times higher toward L-phenylalanine than toward its D-isomer, and this conversion was not inhibited by iproniazid, a specific inhibitor of monoamine oxidase. Under aerobic conditions, rose petal AADC stoichiometrically produced NH3 together with phenylacetaldehyde during the course of decarboxylation and oxidation, followed by the hydrolysis of L-phenylalanine. Phenylacetaldehyde was subsequently converted to 2-phenylethanol by the action of PAR. PAR showed specificity toward several volatile aldehydes. 相似文献