全文获取类型
收费全文 | 799篇 |
免费 | 48篇 |
出版年
2023年 | 9篇 |
2022年 | 4篇 |
2021年 | 18篇 |
2020年 | 18篇 |
2019年 | 21篇 |
2018年 | 15篇 |
2017年 | 10篇 |
2016年 | 33篇 |
2015年 | 39篇 |
2014年 | 42篇 |
2013年 | 65篇 |
2012年 | 60篇 |
2011年 | 80篇 |
2010年 | 46篇 |
2009年 | 36篇 |
2008年 | 43篇 |
2007年 | 37篇 |
2006年 | 35篇 |
2005年 | 29篇 |
2004年 | 39篇 |
2003年 | 36篇 |
2002年 | 39篇 |
2001年 | 11篇 |
2000年 | 14篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1971年 | 4篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1966年 | 1篇 |
1963年 | 1篇 |
1961年 | 2篇 |
1959年 | 1篇 |
1956年 | 2篇 |
排序方式: 共有847条查询结果,搜索用时 33 毫秒
1.
2.
Cristiana Leite N. Tatiana Silva Sandrine Mendes Andreia Ribeiro Joana Paes de Faria Tania Louren?o Francisco dos Santos Pedro Z. Andrade Carla M. P. Cardoso Margarida Vieira Artur Paiva Cláudia L. da Silva Joaquim M. S. Cabral Jo?o B. Relvas Mário Gr?os 《PloS one》2014,9(10)
Mesenchymal stem cells (MSCs) are viewed as safe, readily available and promising adult stem cells, which are currently used in several clinical trials. Additionally, their soluble-factor secretion and multi-lineage differentiation capacities place MSCs in the forefront of stem cell types with expected near-future clinical applications. In the present work MSCs were isolated from the umbilical cord matrix (Wharton''s jelly) of human umbilical cord samples. The cells were thoroughly characterized and confirmed as bona-fide MSCs, presenting in vitro low generation time, high proliferative and colony-forming unit-fibroblast (CFU-F) capacity, typical MSC immunophenotype and osteogenic, chondrogenic and adipogenic differentiation capacity. The cells were additionally subjected to an oligodendroglial-oriented step-wise differentiation protocol in order to test their neural- and oligodendroglial-like differentiation capacity. The results confirmed the neural-like plasticity of MSCs, and suggested that the cells presented an oligodendroglial-like phenotype throughout the differentiation protocol, in several aspects sharing characteristics common to those of bona-fide oligodendrocyte precursor cells and differentiated oligodendrocytes. 相似文献
3.
Sofía Mira‐Martínez Núria Rovira‐Graells Valerie M. Crowley Lindsey M. Altenhofen Manuel Llinás Alfred Cortés 《Cellular microbiology》2013,15(11):1913-1923
Malaria parasites induce changes in the permeability of the infected erythrocyte membrane to numerous solutes, including toxic compounds. In Plasmodium falciparum, this is mainly mediated by PSAC, a broad‐selectivity channel that requires the product of parasite clag3 genes for its activity. The two paralogous clag3 genes, clag3.1 and clag3.2, can be silenced by epigenetic mechanisms and show mutually exclusive expression. Here we show that resistance to the antibiotic blasticidin S (BSD) is associated with switches in the expression of these genes that result in altered solute uptake. Low concentrations of the drug selected parasites that switched from clag3.2 to clag3.1 expression, implying that expression of one or the other clag3 gene confers different transport efficiency to PSAC for some solutes. Selection with higher BSD concentrations resulted in simultaneous silencing of both clag3 genes, which severely compromises PSAC formation as demonstrated by blocked uptake of other PSAC substrates. Changes in the expression of clag3 genes were not accompanied by large genetic rearrangements or mutations at the clag3 loci or elsewhere in the genome. These resultsdemonstrate that malaria parasites can become resistant to toxic compounds such as drugs by epigenetic switches in the expression of genes necessary for the formation of solute channels. 相似文献
4.
5.
Incubation of 14C-labeled substrates continues to be a widely used procedure in soil organic matter (OM) research due to its sensitiveness. When the labeling is found in liquid fractions (soil extracts, hydrolysates), 14C can be easily quantified by using an aliquot for scintillation counting. For this reason, converting a solid carbon sample into liquid form is a typical step for accurate 14C analysis. We have developed an alternative method to carry out this step, which uses standard glass hardware and does not require complex laboratory facilities. Carbon (both in organic or inorganic forms) is converted into CO2 within a reaction vessel connected to a Twisselmann’s extractor with an alkali trap inside. This forms an individual closed chamber (ICC) for each sample, thus eliminating the risk of cross-contaminations. The alkali solution adsorbs the evolved CO2 within the closed system, and the excess of pressure is easily overcome by the use of a balloon. We tested the procedure on a set of substrates and two contrasting soils, checking also the effect of different sample loads (from 20 to 160 mg C) on the CO2 recovery of the process. The percentage of carbon recovered into the alkali (i.e. the efficiency of the process) ranged from 92% for the inorganic C to 93–95% for the organic C method, the latter being sensitive to the amount of sample used for analysis. The ICC method can be successfully applied to analyze 14C-labeling in both carbonates and OM from solid samples, thus representing an alternative method to some established protocols, and it is suitable for substrates with low or very low 14C contents, in which high volumes of sample must be analyzed in order to guarantee representative results. 相似文献
6.
Masaki Unno Albert Ardèvol Carme Rovira Masao Ikeda-Saito 《The Journal of biological chemistry》2013,288(48):34443-34458
Heme oxygenase catalyzes the degradation of heme to biliverdin, iron, and carbon monoxide. Here, we present crystal structures of the substrate-free, Fe3+-biliverdin-bound, and biliverdin-bound forms of HmuO, a heme oxygenase from Corynebacterium diphtheriae, refined to 1.80, 1.90, and 1.85 Å resolution, respectively. In the substrate-free structure, the proximal and distal helices, which tightly bracket the substrate heme in the substrate-bound heme complex, move apart, and the proximal helix is partially unwound. These features are supported by the molecular dynamic simulations. The structure implies that the heme binding fixes the enzyme active site structure, including the water hydrogen bond network critical for heme degradation. The biliverdin groups assume the helical conformation and are located in the heme pocket in the crystal structures of the Fe3+-biliverdin-bound and the biliverdin-bound HmuO, prepared by in situ heme oxygenase reaction from the heme complex crystals. The proximal His serves as the Fe3+-biliverdin axial ligand in the former complex and forms a hydrogen bond through a bridging water molecule with the biliverdin pyrrole nitrogen atoms in the latter complex. In both structures, salt bridges between one of the biliverdin propionate groups and the Arg and Lys residues further stabilize biliverdin at the HmuO heme pocket. Additionally, the crystal structure of a mixture of two intermediates between the Fe3+-biliverdin and biliverdin complexes has been determined at 1.70 Å resolution, implying a possible route for iron exit. 相似文献
7.
Aims
Shrub encroachment in mesic grasslands alters the identity and quality of litters entering the system. As litter from shrubs and grasses can differ in their quality, this can lead to differences in litter decomposition by the direct effect of quality, but also to litter interaction during decomposition. The objective of this study was to examine the occurrence of non-additive effects of litter mixtures on the decomposition rates of legume shrub litter (poor in P) or conifer shrub litter (poor in N) and grass litter.Methods
In addition to single litter type litterbags for the three species, we mixed litters of each pair of possible combinations to determine the influence of each species on mass loss. Litterbags were placed in the field and collected after 1, 6, 8, 12 and 24 months. In each collection, litter of each species remaining in mixed bags was separated, dry weighed and analyzed for C, N and P.Results
With respect to shrub litter decomposing alone, mass loss of shrub litter when mixed with grass showed a 9–10 % increase in decomposition rate for conifer and a 3 % increase for legume litter. These litter mixture effects varied with time and they were detected after a decomposition period of 1 year in legume litter and of 2 years in conifer litter.Conclusions
Grass litter hastened conifer and legume litter decomposition in leaf litter mixtures, at least during the first stages of the process. The potential consequences of this result to alter litter accumulation patterns and thus carbon sequestration rates after shrub encroachment into grasslands will depend on whether the observed trends are maintained in the advanced decomposition stages. 相似文献8.
9.
Susana Isabel Ferreira Luís Miguel Pires José Ferrão Joaquim Sá Armando Serra Isabel Marques Carreira 《Gene》2013
Fragile X syndrome is caused by the expansion of an unstable CGG repeat in the 5′UTR of FMR1 gene. The occurrence of mosaicism is not uncommon, especially in male patients, whereas in females it is not so often reported. Here we report a female foetus that was subject to prenatal diagnosis, because of her mother being a premutation carrier. The foetus was identified as being a mosaic for an intermediate allele and a full mutation of FMR1 gene, in the presence of a normal allele. The mosaic status was confirmed in three different tissues of the foetus – amniotic fluid, skin biopsy and blood – the last two obtained after pregnancy termination. Karyotype analysis and X-chromosome STR markers analysis do not support the mosaicism as inheritance of both maternal alleles. Oligonucleotide array-CGH excluded an imbalance that could contain the primer binding site with a different repeat size. The obtained results give compelling evidence for a postzygotic expansion mechanism where the foetus mosaic pattern originated from expansion of the mother's premutation into a full mutation and consequent regression to an intermediate allele in a proportion of cells. These events occurred in early embryogenesis before the commitment of cells into the different tissues, as the three tested tissues of the foetus have the same mosaic pattern. The couple has a son with Fragile X mental retardation syndrome and choose to terminate this pregnancy after genetic counselling. 相似文献
10.
Maria Mercedes Nogueras Immaculada Pons Ana Ortu?o Jaime Miret Julia Pla Joaquim Castellà Ferran Segura 《PloS one》2013,8(8)