全文获取类型
收费全文 | 1325篇 |
免费 | 96篇 |
出版年
2023年 | 12篇 |
2022年 | 25篇 |
2021年 | 45篇 |
2020年 | 25篇 |
2019年 | 45篇 |
2018年 | 40篇 |
2017年 | 39篇 |
2016年 | 57篇 |
2015年 | 89篇 |
2014年 | 106篇 |
2013年 | 91篇 |
2012年 | 102篇 |
2011年 | 103篇 |
2010年 | 57篇 |
2009年 | 58篇 |
2008年 | 60篇 |
2007年 | 72篇 |
2006年 | 62篇 |
2005年 | 62篇 |
2004年 | 54篇 |
2003年 | 54篇 |
2002年 | 46篇 |
2001年 | 10篇 |
2000年 | 21篇 |
1999年 | 21篇 |
1998年 | 12篇 |
1997年 | 12篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 8篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1956年 | 1篇 |
1928年 | 1篇 |
排序方式: 共有1421条查询结果,搜索用时 15 毫秒
81.
Understanding mechanisms of novel gene expression in polyploids 总被引:40,自引:0,他引:40
Osborn TC Pires JC Birchler JA Auger DL Chen ZJ Lee HS Comai L Madlung A Doerge RW Colot V Martienssen RA 《Trends in genetics : TIG》2003,19(3):141-147
Polyploidy has long been recognized as a prominent force shaping the evolution of eukaryotes, especially flowering plants. New phenotypes often arise with polyploid formation and can contribute to the success of polyploids in nature or their selection for use in agriculture. Although the causes of novel variation in polyploids are not well understood, they could involve changes in gene expression through increased variation in dosage-regulated gene expression, altered regulatory interactions, and rapid genetic and epigenetic changes. New research approaches are being used to study these mechanisms and the results should provide a more complete understanding of polyploidy. 相似文献
82.
Tselios T Daliani I Probert L Deraos S Matsoukas E Roy S Pires J Moore G Matsoukas J 《Bioorganic & medicinal chemistry》2000,8(8):1903-1909
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory and demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). In the present report, a linear analogue and a series of cyclic semi-mimetic peptides were designed and synthesized based on the human myelin basic protein (MBP(87-99)) epitope (Val87-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro90) and on Copolymer I (a mixture of random polymers of Ala, Gln, Lys and Tyr used to treat MS). These analogues were designed looking for suppressors of EAE induced by guinea pig MBP(72-85) epitope (Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-Pro-Val) in Lewis rats. The linear analogue [Arg91,Ala96]MBP(87-99), in which Arg substitutes Lys91 and Ala substitutes Pro96, was found to be a strong inhibitor which when administered to Lewis rats together with the encephalitogenic agonist MBP(72-85) completely prevented the induction of EAE. In contrast, three N- and C-termini amide-linked cyclic semi-mimetic peptides, [cyclo-Phe-Arg-Asn-Ile-Val-Thr-Ala-Acp (1), cyclo-Phe-Ala-Arg-Gln-Acp (2), cyclo-Tyr-Ala-Lys-Gln-Acp (3)] as well as a Lys side chain and C-terminous cyclic semi mimetic peptide cyclo(Lys, Acp)-Phe-Lys-Asn-Ile-Val-Thr-Ala-Acp (4) which contain segments of MBP(87-99) or are constituted from immunophoric residues of copolymer 1, were ineffective in inducing or inhibiting EAE in Lewis rats. However co-injection of cyclic analogues with MBP(72-85) delayed the onset of EAE indicating a modulatory effect on the EAE activity of MBP(72-85). These findings suggest that molecule length, size of cyclic moiety and backbone conformation are important elements for immunogenic activity. Moreover blockade of MBP(72-85) induced EAE by the unrelated peptide [Arg91,Ala56]MBP(87-99) could indicate that the mechanism of inhibition is not due to binding competition but rather due to the delivery of a negative signal by the antagonist which overcomes the agonist response possibly through the activation of antigen specific regulatory T cells. 相似文献
83.
Andrew J. Powell Philip B. Gates Diana Wylie Cristiana P. Velloso Jeremy P. Brockes Parmjit S. Jat 《Experimental cell research》1998,240(2):252
We have exploited a cross-species expression screen to search for cellular immortalizing activities. A newt blastemal cDNA expression library was transfected into rat embryo fibroblasts and immortal cell lines were selected. This identified a 1-kb cDNA fragment which has a low representation in the cDNA library and is derived from the 3′-UTR of an α-glucosidase-related mRNA. Expression of this sequence in rat embryo fibroblasts has shown that it is active in promoting colony formation and immortalization. It is also able to cooperate with an immortalization-defective deletion mutant of SV40 T antigen, indicating that it can exert its growth-stimulatory activity in the pathway activated by a viral immortalizing oncogene. This is the first example of an immortalizing activity mediated by an RNA sequence, and further analysis of its mechanism should provide new insights into senescence and immortalization. 相似文献
84.
M. C. V. Egas M. S. da Costa Don A. Cowan Euclides M. V. Pires 《Extremophiles : life under extreme conditions》1998,2(1):23-32
An extracellular α-amylase produced by the thermophilic bacterium Thermus filiformis Ork A2 was purified from cell-free culture supernatant by ion exchange chromatography. The molecular mass was estimated to
be 60 000 Da by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme was rich in both basic and hydrophobic
amino acids, presenting the following NH2-terminal amino acid sequence: Thr-Ala-Asp-Leu-Ile-Val-Lys-Ile-Asn-Phe. Amylolytic activity on soluble starch was optimal
at pH 5.5–6.0 and 95°C, and the enzyme was stable in the pH range of 4.0–8.0. Calcium enhanced thermostability at temperatures
above 80°C, increasing the half-life of activity to more than 8 h at 85°C, 80 min at 90°C, and 19 min at 95°C. Ethylenediaminetetraacetic
acid (EDTA) inhibited amylase activity, the inhibition being reversed by the addition of calcium or strontium ions. The α-amylase
was also inhibited by copper and mercuric ions, and p-chloromercuribenzoic acid, the latter being reversed in the presence of dithiothreitol. Dithiothreitol and β-mercaptoethanol
activated the enzyme. The α-amylase exhibited Michaelis-Menten kinetics for starch, with a K
m of 5.0 mg·ml−1 and k
cat/K
m of 5.2 × 105 ml·mg−1 s−1. Similar values were obtained for amylose, amylopectin, and glycogen. The hydrolysis pattern was similar for maltooligosaccharides
and polysaccharides, with maltose being the major hydrolysis product. Glucose and maltotriose were generated as secondary
products, although glucose was produced in high levels after a 6-h digestion. To our knowledge this is the first report of
the characterization of an α-amylase from a strain of the genus Thermus.
Received: June 2, 1997 / Accepted: September 16, 1997 相似文献
85.
Reactions of the adduct UCl3·(THF)x (THF = tetrahydrofuran) with compounds of the type K[HnBL4?n], where L = pyrazole or 3,5-dimethylpyrazole, are presented. Based on the results obtained the two compounds UCl2H2BPz2·THF and UCl2HBPz3·THF were isolated. 相似文献
86.
Ana Sílvia Franco Pinheiro Moreira José Pires de Lemos Filho Gerhard Zotz Rosy Mary dos Santos Isaias 《Flora》2009,204(8):604-611
This study compares photosynthetic and structural features of Dichaea cogniauxiana and Epidendrum secundum leaves and roots. The diurnal titratable acidity fluctuations indicated crassulacean acid metabolism (CAM) in E. secundum leaves, associated with anatomical features like thick cuticle, large and vacuolated cells, and reduced stomata size and frequency. Roots of both species had chloroplasts in their cortical parenchyma. However, neither the roots nor D. cogniauxiana leaves did show tissue sap acidity fluctuations. This indicates C3 metabolism in these organs. This lack of oscillation of organic acids in Epidendrum roots was at odds with a CAM-like 13C ratio, suggesting that in spite of active CO2 fixation in roots during the day, the bulk of carbon is imported from the leaves. Roots of both species showed Fv/Fm, ΔF/Fm′, ETR values similar to reports from other non-foliar photosynthetic organs. Besides reducing root carbon cost, root photosynthesis may also be important by alleviating potential hypoxia, since water-saturated velamen severely impedes the gas exchange between radicular cortex. 相似文献
87.
Débora P. Paula Benjamin Linard David A. Andow Edison R. Sujii Carmen S. S. Pires Alfried P. Vogler 《Molecular ecology resources》2015,15(4):880-892
DNA methods are useful to identify ingested prey items from the gut of predators, but reliable detection is hampered by low amounts of degraded DNA. PCR‐based methods can retrieve minute amounts of starting material but suffer from amplification biases and cross‐reactions with the predator and related species genomes. Here, we use PCR‐free direct shotgun sequencing of total DNA isolated from the gut of the harlequin ladybird Harmonia axyridis at five time points after feeding on a single pea aphid Acyrthosiphon pisum. Sequence reads were matched to three reference databases: Insecta mitogenomes of 587 species, including H. axyridis sequenced here; A. pisum nuclear genome scaffolds; and scaffolds and complete genomes of 13 potential bacterial symbionts. Immediately after feeding, multicopy mtDNA of A. pisum was detected in tens of reads, while hundreds of matches to nuclear scaffolds were detected. Aphid nuclear DNA and mtDNA decayed at similar rates (0.281 and 0.11 h?1 respectively), and the detectability periods were 32.7 and 23.1 h. Metagenomic sequencing also revealed thousands of reads of the obligate Buchnera aphidicola and facultative Regiella insecticola aphid symbionts, which showed exponential decay rates significantly faster than aphid DNA (0.694 and 0.80 h?1, respectively). However, the facultative aphid symbionts Hamiltonella defensa, Arsenophonus spp. and Serratia symbiotica showed an unexpected temporary increase in population size by 1–2 orders of magnitude in the predator guts before declining. Metagenomics is a powerful tool that can reveal complex relationships and the dynamics of interactions among predators, prey and their symbionts. 相似文献
88.
Dario Presutti Simonetta Santini Beatrice Cardinali Giuliana Papoff Cristiana Lalli Simone Samperna Valentina Fustaino Giuseppe Giannini Giovina Ruberti 《PloS one》2015,10(11)
Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30–40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation are not sufficient to predict a positive response of NSCLC cells to a cocktail of MET and EGFR inhibitors and highlights the importance of identifying more reliable biomarkers to predict the efficacy of treatments in NSCLC patients resistant to EGFR TKI. 相似文献
89.
Brecht Devleesschauwer Juanita A. Haagsma Frederick J. Angulo David C. Bellinger Dana Cole D?rte D?pfer Aamir Fazil Eric M. Fèvre Herman J. Gibb Tine Hald Martyn D. Kirk Robin J. Lake Charline Maertens de Noordhout Colin D. Mathers Scott A. McDonald Sara M. Pires Niko Speybroeck M. Kate Thomas Paul R. Torgerson Felicia Wu Arie H. Havelaar Nicolas Praet 《PloS one》2015,10(12)