全文获取类型
收费全文 | 980篇 |
免费 | 45篇 |
专业分类
1025篇 |
出版年
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 11篇 |
2019年 | 7篇 |
2018年 | 28篇 |
2017年 | 13篇 |
2016年 | 19篇 |
2015年 | 38篇 |
2014年 | 40篇 |
2013年 | 65篇 |
2012年 | 73篇 |
2011年 | 83篇 |
2010年 | 43篇 |
2009年 | 41篇 |
2008年 | 65篇 |
2007年 | 61篇 |
2006年 | 57篇 |
2005年 | 76篇 |
2004年 | 77篇 |
2003年 | 55篇 |
2002年 | 56篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 8篇 |
1995年 | 8篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 1篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有1025条查询结果,搜索用时 0 毫秒
91.
Izabella Solti Krisztian Kvell Gergely Talaber Sara Veto Peter Acs Ferenc Gallyas Jr. Zsolt Illes Katalin Fekete Petra Zalan Arpad Szanto Zita Bognar 《PloS one》2015,10(6)
Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone’s deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes. 相似文献
92.
Lisa Adolfsson Katalin Solymosi Mats X. Andersson áron Keresztes Johan Uddling Beno?t Schoefs Cornelia Spetea 《PloS one》2015,10(1)
Arbuscular mycorrhizal (AM) fungi play a prominent role in plant nutrition by supplying mineral nutrients, particularly inorganic phosphate (Pi), and also constitute an important carbon sink. AM stimulates plant growth and development, but the underlying mechanisms are not well understood. In this study, Medicago truncatula plants were grown with Rhizophagus irregularis BEG141 inoculum (AM), mock inoculum (control) or with Pi fertilization. We hypothesized that AM stimulates plant growth through either modifications of leaf anatomy or photosynthetic activity per leaf area. We investigated whether these effects are shared with Pi fertilization, and also assessed the relationship between levels of AM colonization and these effects. We found that increased Pi supply by either mycorrhization or fertilization led to improved shoot growth associated with increased nitrogen uptake and carbon assimilation. Both mycorrhized and Pi-fertilized plants had more and longer branches with larger and thicker leaves than the control plants, resulting in an increased photosynthetically active area. AM-specific effects were earlier appearance of the first growth axes and increased number of chloroplasts per cell section, since they were not induced by Pi fertilization. Photosynthetic activity per leaf area remained the same regardless of type of treatment. In conclusion, the increase in growth of mycorrhized and Pi-fertilized Medicago truncatula plants is linked to an increase in the surface for sunlight capture, hence increasing their photosynthetic production, rather than to an increase in the photosynthetic activity per leaf area. 相似文献
93.
94.
János Galambos Gábor Wágner Katalin Nógrádi Attila Bielik László Molnár Amrita Bobok Attila Horváth Béla Kiss Sándor Kolok József Nagy Dalma Kurkó Mónika L. Bakk Mónika Vastag Katalin Sághy István Gyertyán Krisztina Gál István Greiner Zsolt Szombathelyi György M. Keserű György Domány 《Bioorganic & medicinal chemistry letters》2010,20(15):4371-4375
Hit-to-lead optimization of a HTS hit led to new carbamoyloxime derivatives. After identification of an advanced hit (8d) the CYP enzyme inhibitory activity of this class of compounds was successfully eliminated. Systematic exploration of different parts of the advanced hit led us to some promising lead compounds with mGluR5 affinities comparable to that of MPEP. 相似文献
95.
Gábor Wágner Csaba Wéber Olga Nyéki Katalin Nógrádi Attila Bielik László Molnár Amrita Bobok Attila Horváth Béla Kiss Sándor Kolok József Nagy Dalma Kurkó Krisztina Gál István Greiner Zsolt Szombathelyi György M. Keserű György Domány 《Bioorganic & medicinal chemistry letters》2010,20(12):3737-3741
Here we report the discovery and early SAR of a series of mGluR5 negative allosteric modulators (NAMs). Starting from a moderately active HTS hit we synthesized 3,5-disubstituted-oxadiazoles and tetrazoles as mGluR5 NAMs. Based on the analysis of ligand efficiency and lipophilic efficiency metrics we identified a promising lead candidate as a starting point for further optimization. 相似文献
96.
Molnár Miklós Horváth Katalin Dankó Tamás Somlyai Ildikó Kovács Beáta Zs. Somlyai Gábor 《Molecular and cellular biochemistry》2021,476(12):4507-4516
Molecular and Cellular Biochemistry - Deuterium (D) is a stable isotope of hydrogen (H) with a mass number of 2. It is present in natural waters in the form of HDO, at a concentration of... 相似文献
97.
98.
Szilvia Kusza Katalin Priskin Ante Ivankovic Bogumila Jedrzejewska Tomasz Podgorski András Jávor Sándor Mihók 《Biological journal of the Linnean Society. Linnean Society of London》2013,109(1):54-65
The aim of this work was to gather information about the origin and genetic characterization of the Central European Hucul horse based on 71 horses using 17 microsatellites and the D‐loop region of mtDNA. Their genetic relationship to the Polish Konik (N = 7), German (N = 4) and Hungarian wild Przewalski horses (N = 4) and 200 horse sequences from GenBank was also analysed. Both microsatellite and mtDNA analysis showed a high genetic variation in the Hucul. A total of 130 alleles were detected, the mean number of observed alleles per microsatellite was 7.647, and the number of effective alleles was 4.401. The average observed and expected heterozygosity were 0.706 and 0.747, respectively. The high heterozygosity values and Wright's fixation index (FIS) (?0.128) indicated a low level of inbreeding, low or no selection pressure, and large number of alleles. mtDNA analysis revealed 18 haplotypes for the Hucul population with a total of 23 variable sites. Haplotype and nucleotide diversities were 0.935 ± 0.011 and 0.022 ± 0.012, respectively. Neutrality tests (Tajima's D and Fu's Fs) were non‐significant, and mismatch distribution was ragged, indicating that the Hucul population is in genetic equilibrium. The most frequent mtDNA D‐loop region belonged to haplogroup A (48%), which was also present in Przewalski Wild horse samples, while Polish Konik samples belonged to three haplotypes and C, F, and G haplogroups. Large and significant pairwise ΦST values along with a small number of common haplotypes indicated a low level of gene flow and lack of genetic structure among the three studied breeds (Hucul, Konik, and Przewalski Wild horse). The present work contributes to our knowledge of the genetic diversity of the Hucul horse and helps to define its genetic conservation. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 54–65. 相似文献
99.
Modular broad-host-range expression vectors for single-protein and protein complex purification 总被引:1,自引:0,他引:1
Fodor BD Kovács AT Csáki R Hunyadi-Gulyás E Klement E Maróti G Mészáros LS Medzihradszky KF Rákhely G Kovács KL 《Applied and environmental microbiology》2004,70(2):712-721
A set of modular broad-host-range expression vectors with various affinity tags (six-His-tag, FLAG-tag, Strep-tag II, T7-tag) was created. The complete nucleotide sequences of the vectors are known, and these small vectors can be mobilized by conjugation. They are useful in the purification of proteins and protein complexes from gram-negative bacterial species. The plasmids were easily customized for Thiocapsa roseopersicina, Rhodobacter capsulatus, and Methylococcus capsulatus by inserting an appropriate promoter. These examples demonstrate the versatility and flexibility of the vectors. The constructs harbor the T7 promoter for easy overproduction of the desired protein in an appropriate Escherichia coli host. The vectors were useful in purifying different proteins from T. roseopersicina. The FLAG-tag-Strep-tag II combination was utilized for isolation of the HynL-HypC2 protein complex involved in hydrogenase maturation. These tools should be useful for protein purification and for studying protein-protein interactions in a range of bacterial species. 相似文献
100.
Pacifastin protease inhibitors are small cysteine-rich motifs of approximately 35 residues that were discovered in arthropods. The family is divided into two related groups on the basis of the composition of their minimalist inner core. In group I, the core is governed by a Lys10-Trp26 interaction, while in group II it is organized around Phe10. Group I inhibitors exhibit intriguing taxon specificity: potent arthropod-trypsin inhibitors from this group are almost inactive against vertebrate enzymes. The group I member SGPI-1 and the group II member SGPI-2 are extensively studied inhibitors. SGPI-1 is taxon-selective, while SGPI-2 is not. Individual mutations failed to explain the causes underlying this difference. We deciphered this phenomenon using comprehensive combinatorial mutagenesis and phage display. We produced a complete chimeric SGPI-1 / SGPI-2 inhibitor-phage library, in which the two sequences were shuffled at the highest possible resolution of individual residues. The library was selected for binding to bovine trypsin and crayfish trypsin. Sequence analysis of the selectants revealed that taxon specificity is due to an intra-molecular functional coupling between a surface loop and the Lys10-Trp26 core. Five SGPI-2 surface residues transplanted into SGPI-1 resulted in a variant that retained the "taxon-specific" core, but potently inhibited both vertebrate and arthropod enzymes. An additional rational point mutation resulted in a picomolar inhibitor of both trypsins. Our results challenge the generally accepted view that surface residues are the exclusive source of selectivity for canonical inhibitors. Moreover, we provide important insights into general principles underlying the structure-function properties of small disulfide-rich polypeptides, molecules that exist at the borderline between peptides and proteins. 相似文献