全文获取类型
收费全文 | 4393篇 |
免费 | 348篇 |
国内免费 | 1篇 |
出版年
2023年 | 25篇 |
2022年 | 34篇 |
2021年 | 124篇 |
2020年 | 68篇 |
2019年 | 90篇 |
2018年 | 94篇 |
2017年 | 87篇 |
2016年 | 180篇 |
2015年 | 245篇 |
2014年 | 248篇 |
2013年 | 351篇 |
2012年 | 361篇 |
2011年 | 356篇 |
2010年 | 217篇 |
2009年 | 165篇 |
2008年 | 270篇 |
2007年 | 267篇 |
2006年 | 278篇 |
2005年 | 211篇 |
2004年 | 190篇 |
2003年 | 158篇 |
2002年 | 130篇 |
2001年 | 55篇 |
2000年 | 53篇 |
1999年 | 41篇 |
1998年 | 33篇 |
1997年 | 28篇 |
1996年 | 19篇 |
1995年 | 27篇 |
1994年 | 25篇 |
1993年 | 18篇 |
1992年 | 18篇 |
1991年 | 27篇 |
1990年 | 22篇 |
1989年 | 24篇 |
1988年 | 27篇 |
1987年 | 20篇 |
1986年 | 8篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1978年 | 8篇 |
1976年 | 6篇 |
1973年 | 12篇 |
1972年 | 7篇 |
1971年 | 9篇 |
1968年 | 5篇 |
1966年 | 5篇 |
排序方式: 共有4742条查询结果,搜索用时 46 毫秒
991.
Liljana Gentschew Femke‐Anouska Heinsen Amke Caliebe Lene Christiansen Marianne Nygaard Kaare Christensen Hélène Blanché Jean‐François Deleuze Céline Derbois Pilar Galan Carsten Büning Stephan Brand Anette Peters Konstantin Strauch Martina Müller‐Nurasyid Per Hoffmann Markus M. Nöthen Wolfgang Lieb Andre Franke Stefan Schreiber Almut Nebel 《Aging cell》2016,15(3):585-588
Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long‐lived individuals (LLI) and 8919 younger controls. First, we performed a large‐scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune‐associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip‐wide significant signal (PImmunochip = 7.01 × 10–9) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PImmunochip < 5 × 10–4 for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta‐analysis of the combined French and Danish data after adjusting for multiple testing. In a meta‐analysis of all three samples, rs2706372 reached a P‐value of PImmunochip+Repl = 5.42 × 10?7 (OR = 1.20; 95% CI = 1.12–1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. 相似文献
992.
Luana Lugini Cristina Federici Martina Borghi Tommaso Azzarito Maria Lucia Marino Albino Cesolini 《Journal of enzyme inhibition and medicinal chemistry》2016,31(4):538-545
Context: Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy.Objective: To compare the anti-tumor efficacy of different PPIs in vitro and in vivo.Materials and methods: In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice.Results: Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation.Discussion: These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole.Conclusion: The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation. 相似文献
993.
Silvia Castagnaro Camilla Pellegrini Massimo Pellegrini Martina Chrisam Patrizia Sabatelli Silvia Toni 《Autophagy》2016,12(12):2484-2495
A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients. 相似文献
994.
995.
Witarsa Freddy Lansing Stephanie Yarwood Stephanie Gonzalez Mateu Martina 《Applied microbiology and biotechnology》2016,100(22):9795-9806
Applied Microbiology and Biotechnology - The methanogenic communities in alternative inocula and their potential to increase CH4 production in mesophilic and psychrophilic dairy manure-based... 相似文献
996.
997.
998.
IDENTIFICATION OF THE FGL‐AMIDE ALLATOSTATIN GENE OF THE PRIMITIVE TERMITE Mastotermes darwiniensis AND THE WOODROACH Cryptocercus darwini 下载免费PDF全文
Franziska Wende Martina Meyering‐Vos Klaus H. Hoffmann 《Archives of insect biochemistry and physiology》2016,91(2):88-108
Allatostatins with the C‐terminal ending Tyr/Phe‐Xaa‐Phe‐Gly‐Leu/Ile‐amide (FGLa/ASTs) are widespread neuropeptides with multiple functions. The gene encoding the FGLa/AST polypeptide precursor was first isolated from cockroaches and since then could be identified in many insects and crustaceans. With its strictly conserved regions in combination with variable regions the gene seems to be a good candidate for phylogenetic analyses between closely and distantly related species. Here, the structure of the FGLa/AST gene of the most primitive termite, the giant northern termite Mastotermes darwiniensis Froggatt, was identified. The FGLa/AST gene of the woodroach Cryptocercus darwini was also determined. Precursor sequences of both species possess the general organization of dictyopteran FGLa/AST precursors containing 14 putative FGLa/AST peptides. In M. darwiniensis, only 11 out of the 14 FGLa/AST‐like peptides possess the C‐terminal conserved region Y/FXFGL/I/V/M and four of the putative peptide structures are not followed by a Gly residue that would lead to nonamidated peptides. Phylogenetic analyses show the high degree of similarity of dictyopteran FGLa/AST sequences. The position of termites, nested within the Blattaria, confirms that termites have evolved from primitive cockroaches. 相似文献
999.
Tania Di Raimo Martina Leopizzi Giorgio Mangino Carlo Della Rocca Rita Businaro Lucia Longo Vincenza Rita Lo Vasco 《Journal of cell communication and signaling》2016,10(4):283-293
Macrophages’ phenotypic and functional diversity depends on differentiating programs related to local environmental factors. Recent interest was deserved to the signal transduction pathways acting in macrophage polarization, including the phosphoinositide (PI) system and related phospholipase C (PLC) family of enzymes. The expression panel of PLCs and the subcellular localization differs in quiescent cells compared to the pathological counterpart. We analyzed the expression of PLC enzymes in unpolarized (M0), as well as in M1 and M2 macrophages to list the expressed isoforms and their subcellular localization. Furthermore, we investigated whether inflammatory stimulation modified the basal panel of PLCs’ expression and subcellular localization. All PLC enzymes were detected within both M1 and M2 cells, but not in M0 cells. M0, as well as M1 and M2 cells own a specific panel of expression, different for both genes’ mRNA expression and intracellular localization of PLC enzymes. The panel of PLC genes’ expression and PLC proteins’ presence slightly changes after inflammatory stimulation. PLC enzymes might play a complex role in macrophages during inflammation and probably also during polarization. 相似文献
1000.
Elham Alizadeh Pasdar Michael Smits Michael Stapelberg Martina Bajzikova Marina Stantic Jacob Goodwin Bing Yan Jan Stursa Jaromira Kovarova Karishma Sachaphibulkij Ayenachew Bezawork-Geleta Margaryta Sobol Anatoly Filimonenko Marco Tomasetti Renata Zobalova Pavel Hozak Lan-Feng Dong Jiri Neuzil 《PloS one》2016,11(5)