全文获取类型
收费全文 | 978篇 |
免费 | 38篇 |
国内免费 | 7篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 22篇 |
2020年 | 21篇 |
2019年 | 14篇 |
2018年 | 19篇 |
2017年 | 21篇 |
2016年 | 31篇 |
2015年 | 46篇 |
2014年 | 44篇 |
2013年 | 57篇 |
2012年 | 69篇 |
2011年 | 73篇 |
2010年 | 34篇 |
2009年 | 41篇 |
2008年 | 43篇 |
2007年 | 46篇 |
2006年 | 38篇 |
2005年 | 37篇 |
2004年 | 65篇 |
2003年 | 45篇 |
2002年 | 40篇 |
2001年 | 13篇 |
2000年 | 17篇 |
1999年 | 11篇 |
1998年 | 10篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有1023条查询结果,搜索用时 375 毫秒
241.
Protease is one of the most important industrial enzymes with a multitude of applications in both food and non-food sectors. Although most commercial proteases are microbial proteases, the potential of non-conventional protease sources, especially plants, should not be overlooked. In this study, horse mango (Mangifera foetida Lour) fruit, known to produce latex with a blistering effect upon contact with human skin, was chosen as a source of protease, and the effect of the extraction process on its protease activity evaluated. The crude enzyme was extracted from the kernels and extraction was optimized by a response surface methodology (RSM) using a central composite rotatable design (CCRD). The variables studied were pH (x(1)), CaCl(2) (x(2)), Triton X-100 (x(3)), and 1,4-dithryeitol (x(4)). The results obtained indicate that the quadratic model is significant for all the variables tested. Based on the RSM model generated, optimal extraction conditions were obtained at pH 6.0, 8.16 mM CaCl(2), 5.0% Triton X-100, and 10.0 mM DTT, and the estimated response was 95.5% (w/w). Verification test results showed that the difference between the calculated and the experimental protease activity value was only 2%. Based on the t-value, the effects of the variables arranged in ascending order of strength were CaCl(2)< pH < DTT < Triton X-100. 相似文献
242.
In this review, we focus on pathways intersecting through p53 and cyclin E, highlighting how oncogenic effects of cyclin E deregulation, especially overexpression of shortened or low molecular weight (LMW) forms of cyclin E protein, are amplified by loss of regulatory control through p53 to promote tumor development. Expression of cyclin E protein promotes progression into S-phase, an activity opposed by p53-regulated activation of checkpoint controls or apoptosis. Loss of p53 function is an escape hatch by which tumor cells, initiated by a number of means including cyclin E deregulation, can avoid cell cycle arrest or cell death and progress through further stages of unchecked deregulation and growth. To determine how this escape hatch is opened and, ultimately, how to close it, we must understand the networks of normal signaling and processing in a cell and where they intersect. 相似文献
243.
Selection of nonapoptotic spermatozoa as a new tool for enhancing assisted reproduction outcomes: an in vitro model 总被引:2,自引:0,他引:2
Said T Agarwal A Grunewald S Rasch M Baumann T Kriegel C Li L Glander HJ Thomas AJ Paasch U 《Biology of reproduction》2006,74(3):530-537
Magnetic cell sorting (MACS) using annexin V-conjugated microbeads eliminates apoptotic spermatozoa based on the externalization of phosphatidylserine residues. The procedure delivers two sperm fractions: annexin V-negative (nonapoptotic) and annexin V-positive (apoptotic). Our aim was to determine whether the sperm fertilizing potential can be improved by selecting a nonapoptotic fraction using MACS. Semen samples (n = 35) were subjected to separation on a density gradient followed by MACS. Extent of apoptosis was assessed by measuring levels of activated caspase 3 using fluorescein-labeled inhibitors of caspase, alterations in mitochondrial membrane potential (MMP) using a lipophilic cationic dye, and DNA fragmentation using terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling assay. The sperm fertilization potential was assessed using hamster oocyte penetration assay and hamster oocyte-intracytoplasmic sperm injection (ICSI). Annexin V-negative sperm displayed superior quality in terms of high motility, low caspase 3 activation, MMP integrity, and small extent of DNA fragmentation. Annexin V-negative sperm demonstrated higher oocyte penetration capacity but comparable sperm chromatin decondensation (SCD) following ICSI. Conversely, the annexin V-positive sperm presented with poor quality and fertilization potential. The oocyte penetration rate was negatively correlated with apoptotic marker expression, whereas SCD following ICSI was only associated with apoptosis on sperm-damaged membranes. We conclude that apoptosis appears to impact sperm-oocyte penetration rate; however, it does not seem to affect early stages of fertilization such as SCD in spermatozoa of healthy donors. The selection of nonapoptotic sperm by MACS may be used to enhance results of in vitro fertilization by increasing sperm-oocyte penetration. 相似文献
244.
25-hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR 总被引:2,自引:0,他引:2
Amalia Trousson† Sophie Bernard† Patrice X. Petit‡ Philippe Liere Antoine Pianos Khadija El Hadri§ Jean-Marc A. Lobaccaro¶ M. Said Ghandour Michel Raymondjean§ Michael Schumacher Charbel Massaad† 《Journal of neurochemistry》2009,109(4):945-958
In several neurodegenerative diseases of the CNS, oligodendrocytes are implicated in an inflammatory process associated with altered levels of oxysterols and inflammatory enzymes such as secreted phospholipase A2 (sPLA2). In view of the scarce literature related to this topic, we investigated oxysterol effects on these myelinating glial cells. Natural oxysterol 25-hydroxycholesterol (25-OH; 1 and 10 μM) altered oligodendrocyte cell line (158N) morphology and triggered apoptosis (75% of apoptosis after 72 h). These effects were mimicked by 22( S )-OH (1 and 10 μM) which does not activate liver X receptor (LXR) but not by a synthetic LXR ligand (T0901317). Therefore, oxysterol-induced apoptosis appears to be independent of LXR. Interestingly, sPLA2 type IIA (sPLA2-IIA) over-expression partially rescued 158N cells from oxysterol-induced apoptosis. In fact, 25-OH, 24( S )-OH, and T0901317 stimulated sPLA2-IIA promoter and sPLA2 activity in oligodendrocyte cell line. Accordingly, administration of T0901317 to mice enhanced sPLA2 activity in brain extracts by twofold. Short interfering RNA strategy allowed to establish that stimulation of sPLA2-IIA is mediated by pregnane X receptor (PXR) at high oxysterol concentration (10 μM) and by LXR β at basal oxysterol concentration. Finally, GC coupled to mass spectrometry established that oligodendrocytes contain oxysterols and express their biosynthetic enzymes, suggesting that they may act through autocrine/paracrine mechanism. Our results show the diversity of oxysterol signalling in the CNS and highlight the positive effects of the LXR/PXR pathway which may open new perspectives in the treatment of demyelinating and neurodegenerative diseases. 相似文献
245.
Timothy Coon Wilna J. Moree Binfeng Li Jinghua Yu Said Zamani-Kord Siobhan Malany Mark A. Santos Lisa M. Hernandez Robert E. Petroski Aixia Sun Jenny Wen Sue Sullivan Jason Haelewyn Michael Hedrick Samuel J. Hoare Margaret J. Bradbury Paul D. Crowe Graham Beaton 《Bioorganic & medicinal chemistry letters》2009,19(15):4380-4384
The benzimidazole core of the selective non-brain-penetrating H1-antihistamine mizolastine was used to identify a series of brain-penetrating H1-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H1-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro profile. 相似文献
246.
247.
Daniela Stokmaier Oleg Khorev Brian Cutting Rita Born Daniel Ricklin Thomas O.G. Ernst Fabienne Böni Kathrin Schwingruber Martin Gentner Matthias Wittwer Morena Spreafico Angelo Vedani Said Rabbani Oliver Schwardt Beat Ernst 《Bioorganic & medicinal chemistry》2009,17(20):7254-7264
A series of novel aryl-substituted triazolyl d-galactosamine derivatives was synthesized as ligands for the carbohydrate recognition domain of the major subunit H1 (H1-CRD) of the human asialoglycoprotein receptor (ASGP-R). The compounds were biologically evaluated with a newly developed competitive binding assay, surface plasmon resonance and by a competitive NMR binding experiment. With compound 1b, a new ligand with a twofold improved affinity to the best so far known d-GalNAc was identified. This small, drug-like ligand can be used as targeting device for drug delivery to hepatocytes. 相似文献
248.
Boulila Farida Depret Géraldine Boulila Abdelghani Belhadi Djellali Benallaoua Said Laguerre Gisèle 《Systematic and applied microbiology》2009
Sixty-seven isolates were isolated from nodules collected on roots of Mediterranean shrubby legumes Retama raetam and Retama sphaerocarpa growing in seven ecological–climatic areas of northeastern Algeria. Genetic diversity of the Retama isolates was analyzed based on genotyping by restriction fragment length polymorphism of PCR-amplified fragments of the 16S rRNA gene, the intergenic spacer (IGS) region between the 16S and 23S rRNA genes (IGS), and the symbiotic genes nifH and nodC. Eleven haplotypes assigned to the Bradyrhizobium genus were identified. Significant biogeographical differentiation of the rhizobial populations was found, but one haplotype was predominant and conserved across the sites. All isolates were able to cross-nodulate the two Retama species. Accordingly, no significant genetic differentiation of the rhizobial populations was found in relation to the host species of origin. Sequence analysis of the 16S rRNA gene grouped the isolates with Bradyrhizobium elkanii, but sequence analyses of IGS, the housekeeping genes (dnaK, glnII, recA), nifH, and nodC yielded convergent results showing that the Retama nodule isolates from the northeast of Algeria formed a single evolutionary lineage, which was well differentiated from the currently named species or well-delineated unnamed genospecies of bradyrhizobia. Therefore, this study showed that the Retama species native to northeastern Algeria were associated with a specific clade of bradyrhizobia. The Retama isolates formed three sub-groups based on IGS and housekeeping gene phylogenies, which might form three sister species within a novel bradyrhizobial clade. 相似文献
249.
Said Ennahli Mustapha El Bouhssini Stefania Grando Radhika Anathakrishnan Terutaka Niide Laura Starkus Sharon Starkey C. Michael Smith 《Arthropod-Plant Interactions》2009,3(1):45-53
The Russian wheat aphid Diuraphis noxia (Kurdjumov) (Homoptera: Aphididae) is a global pest of wheat and barley. This arthropod is difficult to manage with pesticides
or biological control agents due to the aphid’s ability to seek shelter in rolled leaves and also to develop virulent biotypes.
During the past 20 years, the use of aphid-resistant cereal cultivars has proven to be an economically and ecologically beneficial
method of protecting crops from D. noxia damage. Our research reports the results of experiments to determine the categories of D. noxia biotype 2 resistance present in Cereal Introduction Triticeae (CItr) 2401, and a barley genotype (IBRWAGP4-7), compared to
control resistant and susceptible wheat and barley genotypes. CItr2401 and IBRWAGP4-7 exhibit no antixenosis, but both genotypes
demonstrated antibiosis to D. noxia in the form of reduced aphid populations. Reduced leaf dry weight change, a measure of plant tolerance of D. noxia feeding, was significantly less in CItr2401 and IBRWAGP4-7 plants than in plants of susceptible control varieties. However,
tolerance was negated when a tolerance index was calculated to correct for differences in aphid populations. Barley IBRWAGP4-7
is a new source of D. noxia biotype 2 resistance. D. noxia foliar leaf damage and population growth were significantly less on IBRWAGP4-7 plants than on plants of the susceptible barley
variety Morex. IBRWAGP4-7 plants were equal in resistance to plants of the resistant barley STARS 9301 and wheat genotype
CItr2401.
Handling editor: Heikki Hokkanen 相似文献
250.
Sophie Javerzat Mélanie Franco John Herbert Natalia Platonova Anne-Lise Peille Véronique Pantesco John De Vos Said Assou Roy Bicknell Andreas Bikfalvi Martin Hagedorn 《PloS one》2009,4(11)