全文获取类型
收费全文 | 686篇 |
免费 | 44篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 15篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 19篇 |
2015年 | 36篇 |
2014年 | 21篇 |
2013年 | 42篇 |
2012年 | 53篇 |
2011年 | 59篇 |
2010年 | 33篇 |
2009年 | 28篇 |
2008年 | 42篇 |
2007年 | 60篇 |
2006年 | 37篇 |
2005年 | 40篇 |
2004年 | 35篇 |
2003年 | 38篇 |
2002年 | 25篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 11篇 |
1995年 | 8篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有730条查询结果,搜索用时 15 毫秒
91.
92.
93.
DM Iglesias R El-Kares A Taranta F Bellomo F Emma M Besouw E Levtchenko J Toelen L van den Heuvel L Chu J Zhao YK Young N Eliopoulos P Goodyer 《PloS one》2012,7(8):e42840
Cystinosis is a rare disease caused by homozygous mutations of the CTNS gene, encoding a cystine efflux channel in the lysosomal membrane. In Ctns knockout mice, the pathologic intralysosomal accumulation of cystine that drives progressive organ damage can be reversed by infusion of wildtype bone marrow-derived stem cells, but the mechanism involved is unclear since the exogeneous stem cells are rarely integrated into renal tubules. Here we show that human mesenchymal stem cells, from amniotic fluid or bone marrow, reduce pathologic cystine accumulation in co-cultured CTNS mutant fibroblasts or proximal tubular cells from cystinosis patients. This paracrine effect is associated with release into the culture medium of stem cell microvesicles (100-400 nm diameter) containing wildtype cystinosin protein and CTNS mRNA. Isolated stem cell microvesicles reduce target cell cystine accumulation in a dose-dependent, Annexin V-sensitive manner. Microvesicles from stem cells expressing CTNS(Red) transfer tagged CTNS protein to the lysosome/endosome compartment of cystinotic fibroblasts. Our observations suggest that exogenous stem cells may reprogram the biology of mutant tissues by direct microvesicle transfer of membrane-associated wildtype molecules. 相似文献
94.
95.
Anand Raj Kumar Kullan Maria M. van Dyk Nicoletta Jones Arnulf Kanzler Arlene Bayley Alexander A. Myburg 《Tree Genetics & Genomes》2012,8(1):163-175
Traits that differentiate cross-fertile plant species can be dissected by genetic linkage analysis in interspecific hybrids.
Such studies have been greatly facilitated in Eucalyptus tree species by the recent development of Diversity Arrays Technology (DArT) markers. DArT is an affordable, high-throughput
marker technology for the construction of high-density genetic linkage maps. Eucalyptus grandis and Eucalyptus urophylla are commonly used to produce fast-growing, disease tolerant hybrids for clonal eucalypt plantations in tropical and subtropical
regions. We analysed 7,680 DArT markers in an F2 pseudo-backcross mapping pedigree based on an F1 hybrid clone of E. grandis and E. urophylla. A total of 2,440 markers (31.7%) were polymorphic and could be placed in linkage maps of the F1 hybrid and two pure-species
backcross parents. An integrated genetic linkage map was constructed for the pedigree resulting in 11 linkage groups (n = 11) with 2,290 high-confidence (LOD ≥ 3.0) markers and a total map length of 1,107.6 cM. DNA sequence analysis of the mapped
DArT marker fragments revealed that 43% were located in protein coding regions and 90% could be placed in the recently completed
draft genome assembly of E. grandis. Together with the anchored genomic sequence information, this linkage map will allow detailed genetic dissection of quantitative
traits and hybrid fitness characters segregating in the F2 progeny and will facilitate the development of markers for molecular
breeding in Eucalyptus. 相似文献
96.
Raffaella Ponassi Barbara Biasotti Valeria Tomati Silvia Bruno Alessandro Poggi Davide Malacarne Guido Cimoli Annalisa Salis Sarah Pozzi Maurizio Miglino Gianluca Damonte Pietro Cozzini Francesca Spyrakis Barbara Campanini Luca Bagnasco Nicoletta Castagnino Lorenzo Tortolina Anna Mumot Francesco Frassoni Antonio Daga Michele Cilli Federica Piccardi Ilaria Monfardini Miriam Perugini Gabriele Zoppoli Cristina D’Arrigo Raffaele Pesenti Silvio Parodi 《Cell cycle (Georgetown, Tex.)》2012,11(19):3703
97.
Characterization of biotin-anandamide, a novel tool for the visualization of anandamide accumulation
Fezza F Oddi S Di Tommaso M De Simone C Rapino C Pasquariello N Dainese E Finazzi-Agrò A Maccarrone M 《Journal of lipid research》2008,49(6):1216-1223
Anandamide (N-arachidonoylethanolamide; AEA) acts as an endogenous agonist of both cannabinoid and vanilloid receptors. During the last two decades, its metabolic pathways and biological activity have been investigated extensively and relatively well characterized. In contrast, at present, the effective nature and mechanism of AEA transport remain controversial and still unsolved issues. Here, we report the characterization of a biotinylated analog of AEA (b-AEA) that has the same lipophilicity of the parent compound. In addition, by means of biochemical assays and fluorescence microscopy, we show that b-AEA is accumulated inside the cells in a way superimposable on that of AEA. Conversely, b-AEA does not interact or interfere with the other components of the endocannabinoid system, such as type-1 and type-2 cannabinoid receptors, vanilloid receptor, AEA synthetase (N-acylphosphatidylethanolamine-hydrolyzing phospholipase D), or AEA hydrolase (fatty acid amide hydrolase). Together, our data suggest that b-AEA could be a very useful probe for visualizing the accumulation and intracellular distribution of this endocannabinoid. 相似文献
98.
99.
100.
Rusconi L Salvatoni L Giudici L Bertani I Kilstrup-Nielsen C Broccoli V Landsberger N 《The Journal of biological chemistry》2008,283(44):30101-30111
Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome (RTT), West syndrome, and X-linked infantile spasms, sharing the common feature of mental retardation and early seizures. CDKL5 is a rather uncharacterized kinase, but its involvement in RTT seems to be explained by the fact that it works upstream of MeCP2, the main cause of Rett syndrome. To understand the role of this kinase for nervous system functions and to address if molecular mechanisms are involved in regulating its distribution and activity, we studied the ontogeny of CDKL5 expression in developing mouse brains by immunostaining and Western blotting. The expression profile of CDKL5 was compared with that of MeCP2. The two proteins share a general expression profile in the adult mouse brain, but CDKL5 levels appear to be highly modulated at the regional level. Its expression is strongly induced in early postnatal stages, and in the adult brain CDKL5 is present in mature neurons, but not in astroglia. Interestingly, the presence of CDKL5 in the cell nucleus varies at the regional level of the adult brain and is developmentally regulated. CDKL5 shuttles between the cytoplasm and the nucleus and the C-terminal tail is involved in localizing the protein to the cytoplasm in a mechanism depending on active nuclear export. Accordingly, Rett derivatives containing disease-causing truncations of the C terminus are constitutively nuclear, suggesting that they might act as gain of function mutations in this cellular compartment. 相似文献