全文获取类型
收费全文 | 2320篇 |
免费 | 180篇 |
国内免费 | 6篇 |
出版年
2022年 | 22篇 |
2021年 | 35篇 |
2020年 | 23篇 |
2019年 | 30篇 |
2018年 | 45篇 |
2017年 | 33篇 |
2016年 | 46篇 |
2015年 | 79篇 |
2014年 | 99篇 |
2013年 | 130篇 |
2012年 | 210篇 |
2011年 | 163篇 |
2010年 | 96篇 |
2009年 | 99篇 |
2008年 | 141篇 |
2007年 | 155篇 |
2006年 | 149篇 |
2005年 | 117篇 |
2004年 | 143篇 |
2003年 | 108篇 |
2002年 | 93篇 |
2001年 | 29篇 |
2000年 | 18篇 |
1999年 | 21篇 |
1998年 | 32篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 19篇 |
1994年 | 25篇 |
1993年 | 26篇 |
1992年 | 17篇 |
1991年 | 20篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 9篇 |
1984年 | 10篇 |
1983年 | 11篇 |
1982年 | 16篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1974年 | 10篇 |
1973年 | 10篇 |
1971年 | 7篇 |
1970年 | 6篇 |
1967年 | 7篇 |
排序方式: 共有2506条查询结果,搜索用时 15 毫秒
201.
Maldonado GE Pérez CA Covarrubias EE Cabriales SA Leyva LA Pérez JC Almaguer DG 《Cytotherapy》2011,13(10):1249-1255
BACKGROUND AIMS. Lymphedema is a common complication with breast cancer treatment that does not have a definite cure. Our objective was to determine the efficacy of autologous stem cells (ASC) in the treatment of lymphedema secondary to mastectomy and axillary lymphadenectomy in comparison with traditional decongestive treatment with compression sleeves. METHODS. A prospective study including 20 women with lymphedema secondary to breast cancer surgery with axillary lymphadenectomy was conducted. Women were assigned at random to one of two groups. One group of 10 women was injected with ASC in the affected arm, whereas the other 10 women comprised the control group and received traditional compression sleeve therapy (CST). The follow-up for both groups was 12 weeks. Pain, sensitivity and mobility were assessed before and after therapy. RESULTS. There was improvement in the volume of lymphedema in both groups, with no significant difference. In the ASC group there was an overall volume reduction during the follow-up, whereas in the CST group lymphedema recurred after the compression sleeve was removed. CONCLUSIONS. Our findings suggest that ASC injection for patients with lymphedema can be an effective treatment. It reduces arm volume and associated co-morbidities of pain and decreased sensitivity. Traditional CST was also effective for lymphedema reduction, but it was dependent on continuous use of the treatment. 相似文献
202.
Pospichalova V Tureckova J Fafilek B Vojtechova M Krausova M Lukas J Sloncova E Takacova S Divoky V Leprince D Plachy J Korinek V 《Genesis (New York, N.Y. : 2000)》2011,49(3):142-151
HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located on chromosome 17p13.3, a region frequently hypermethylated or deleted in human neoplasias. In mouse, Hic1 is essential for embryonic development and exerts an antitumor role in adult animals. Since Hic1-deficient mice die perinatally, we generated a conditional Hic1 null allele by flanking the Hic1-coding region by loxP sites. When crossed to animals expressing Cre recombinase in a cell-specific manner, the Hic1 conditional mice will provide new insights into the function of Hic1 in developing and mature tissues. Additionally, we used gene targeting to replace sequence-encoding amino acids 186-893 of Hic1 by citrine fluorescent protein cDNA. We demonstrate that the distribution of Hic1-citrine fusion polypeptide corresponds to the expression pattern of wild-type Hic1. Consequently, Hic1-citrine "reporter" mice can be used to monitor the activity of the Hic1 locus using citrine fluorescence. 相似文献
203.
During filamentous fungus development, multinucleated hyphae employ a system for long-range nuclear migration to maintain an equal nuclear density. A decade ago the microtubule motor dynein was shown to play a central role in this process. Previous studies with Ashbya gossypii revealed extensive bidirectional movements and bypassings of nuclei, an autonomous cytoplasmic microtubule (cMT) cytoskeleton emanating from each nucleus, and pulling of nuclei by sliding of cMTs along the cortex. Here, we show that dynein is the sole motor for bidirectional movements and bypassing because these movements are concomitantly decreased in mutants carrying truncations of the dynein heavy-chain DYN1 promoter. The dynactin component Jnm1, the accessory proteins Dyn2 and Ndl1, and the potential dynein cortical anchor Num1 are also involved in the dynamic distribution of nuclei. In their absence, nuclei aggregate to different degrees, whereby the mutants with dense nuclear clusters grow extremely long cMTs. As in budding yeast, we found that dynein is delivered to cMT plus ends, and its activity or processivity is probably controlled by dynactin and Num1. Together with its role in powering nuclear movements, we propose that dynein also plays (directly or indirectly) a role in the control of cMT length. Those combined dynein actions prevent nuclear clustering in A. gossypii and thus reveal a novel cellular role for dynein. 相似文献
204.
Iacovache I Degiacomi MT Pernot L Ho S Schiltz M Dal Peraro M van der Goot FG 《PLoS pathogens》2011,7(7):e1002135
Throughout evolution, one of the most ancient forms of aggression between cells or organisms has been the production of proteins or peptides affecting the permeability of the target cell membrane. This class of virulence factors includes the largest family of bacterial toxins, the pore-forming toxins (PFTs). PFTs are bistable structures that can exist in a soluble and a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential to protect the PFT-producing cell. Here we have investigated the folding of aerolysin, produced by the human pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches, we show that the CTP prevents aggregation during biosynthetic folding. We identified specific residues that mediate binding of the CTP to the toxin. We show that the CTP is crucial for the control of the aerolysin activity, since it protects individual subunits from aggregation within the bacterium and later controls assembly of the quaternary pore-forming complex at the surface of the target host cell. The CTP is the first example of a C-terminal chain-linked chaperone with dual function. 相似文献
205.
206.
Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders. 相似文献
207.
van der Poel S Wolthoorn J van den Heuvel D Egmond M Groux-Degroote S Neumann S Gerritsen H van Meer G Sprong H 《Traffic (Copenhagen, Denmark)》2011,12(11):1634-1647
Sphingolipids are considered to play a key role in protein sorting and membrane trafficking. In melanocytic cells, sorting of lysosomal and melanosomal proteins requires the sphingolipid glucosylceramide (GlcCer). This sorting information is located in the lumenal domain of melanosomal proteins. We found that two processes dependent on lumenal pH, protein sialylation and lysosomal acid lipase (LAL) activity were aberrant in GM95 melanocyte cells, which do not produce glycosphingolipids. Using fluorescence lifetime imaging microscopy (FLIM), we found that the lumenal pH in the trans-Golgi network and lysosomes of wild-type melanocyte MEB4 cells are >1 pH unit lower than GM95 cells and fibroblasts. In addition to the lower pH found in vivo, the in vitro activity of the proton pump, the vacuolar-type H(+) -translocating ATPase (V-ATPase), was twofold higher in MEB4 compared to GM95 cells. The apparent K(i) for inhibition of the V-ATPase by concanamycin A and archazolid A, which share a common binding site on the c-ring, was lower in glycosphingolipid-deficient GM95 cells. No difference between the MEB4 and GM95 cells was found for the V-ATPase inhibitors apicularen A and salicylihalimide. We conclude that hyperacidification in MEB4 cells requires glycosphingolipids and propose that low pH is necessary for protein sorting and melanosome biogenesis. Furthermore, we suggest that glycosphingolipids are indirectly involved in protein sorting and melanosome biogenesis by stimulating the proton pump, possibly through binding of GlcCer. These experiments establish, for the first time, a link between pH, glycosphingolipids and melanosome biogenesis in melanocytic MEB4 cells, to suggest a role for glycosphingolipids in hyperacidification in melanocytes. 相似文献
208.
209.
Keith L. McDougall Jake M. Alexander Sylvia Haider Aníbal Pauchard Neville G. Walsh Christoph Kueffer 《Diversity & distributions》2011,17(1):103-111
Aim We use data from 13 mountain regions and surrounding lowland areas to identify (1) the origins, traits and cultural uses of alien plant species that establish in mountains, (2) the alien species that are most likely to be a threat and (3) how managers might use this information to prevent further invasions. Location Australia, Canada, Chile, India, New Zealand, South Africa, Spain, Switzerland, USA. Methods Lists of alien species were compiled for mountains and their surrounding or nearby lowlands. Principal co‐ordinates analysis was performed on a matrix of similarities created using presence/absence data for alien species. The significance of differences between means for (1) similarity metrics of lowland and mountain groups and (2) species traits of lowland and mountain alien floras was determined using t‐tests. In seven of the 13 mountain regions, lists of alien species undergoing management were compiled. The significance of differences between proportions of traits for species requiring and not requiring management input was determined with chi‐square tests. Results We found that the proximal lowland alien flora is the main determinant of a mountain region’s alien species composition. The highest similarities between mountain floras were in the Americas/Pacific Region. The majority of alien species commonly found in mountains have agricultural origins and are of little concern to land managers. Woody species and those used for ornamental purposes will often pose the greatest threat. Main conclusions Given the documented potential threat of alien species invading mountains, we advise natural resource managers to take preventive measures against the risk of alien plant invasion in mountains. A strategy for prevention should extend to the surrounding lowland areas and in particular regulate the introduction of species that are already of management concern in other mountains as well as climatically pre‐adapted alien mountain plants. These may well become more problematic than the majority of alien plants currently in mountains. 相似文献
210.
Bottolo L Chadeau-Hyam M Hastie DI Langley SR Petretto E Tiret L Tregouet D Richardson S 《Bioinformatics (Oxford, England)》2011,27(4):587-588
SUMMARY: ESS++ is a C++ implementation of a fully Bayesian variable selection approach for single and multiple response linear regression. ESS++ works well both when the number of observations is larger than the number of predictors and in the 'large p, small n' case. In the current version, ESS++ can handle several hundred observations, thousands of predictors and a few responses simultaneously. The core engine of ESS++ for the selection of relevant predictors is based on Evolutionary Monte Carlo. Our implementation is open source, allowing community-based alterations and improvements. AVAILABILITY: C++ source code and documentation including compilation instructions are available under GNU licence at http://bgx.org.uk/software/ESS.html. 相似文献