全文获取类型
收费全文 | 706篇 |
免费 | 46篇 |
专业分类
752篇 |
出版年
2021年 | 12篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 5篇 |
2015年 | 25篇 |
2014年 | 33篇 |
2013年 | 36篇 |
2012年 | 47篇 |
2011年 | 47篇 |
2010年 | 37篇 |
2009年 | 24篇 |
2008年 | 42篇 |
2007年 | 38篇 |
2006年 | 32篇 |
2005年 | 30篇 |
2004年 | 45篇 |
2003年 | 35篇 |
2002年 | 30篇 |
2001年 | 14篇 |
2000年 | 15篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 10篇 |
1993年 | 8篇 |
1992年 | 7篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1979年 | 4篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1970年 | 5篇 |
1968年 | 3篇 |
1966年 | 3篇 |
1965年 | 5篇 |
1963年 | 4篇 |
1962年 | 3篇 |
1961年 | 4篇 |
排序方式: 共有752条查询结果,搜索用时 15 毫秒
61.
62.
MOTIVATION: The sequence of artificial genetic constructs is composed of multiple functional fragments, or genetic parts, involved in different molecular steps of gene expression mechanisms. Biologists have deciphered structural rules that the design of genetic constructs needs to follow in order to ensure a successful completion of the gene expression process, but these rules have not been formalized, making it challenging for non-specialists to benefit from the recent progress in gene synthesis. RESULTS: We show that context-free grammars (CFG) can formalize these design principles. This approach provides a path to organizing libraries of genetic parts according to their biological functions, which correspond to the syntactic categories of the CFG. It also provides a framework for the systematic design of new genetic constructs consistent with the design principles expressed in the CFG. Using parsing algorithms, this syntactic model enables the verification of existing constructs. We illustrate these possibilities by describing a CFG that generates the most common architectures of genetic constructs in Escherichia coli. AVAILABILITY: A web site allows readers to experiment with the algorithms presented in this article: www.genocad.org. SUPPLEMENTARY INFORMATION: Sequences and models are available at Bioinformatics online. 相似文献
63.
Species interactions may profoundly influence disease outbreaks. However, disease ecology has only begun to integrate interactions between hosts and their food resources (foraging ecology) despite that hosts often encounter their parasites while feeding. A zooplankton–fungal system illustrated this central connection between foraging and transmission. Using experiments that varied food density for Daphnia hosts, density of fungal spores and body size of Daphnia , we produced mechanistic yet general models for disease transmission rate based on broadly applicable components of feeding biology. Best performing models could explain why prevalence of infection declined at high food density and rose sharply as host size increased (a pattern echoed in nature). In comparison, the classic mass-action model for transmission performed quite poorly. These foraging-based models should broadly apply to systems in which hosts encounter parasites while eating, and they will catalyse future integration of the roles of Daphnia as grazer and host. 相似文献
64.
Cynthia E. Vargas García Mariya Petrova Ingmar J. J. Claes Ilke De Boeck Tine L. A. Verhoeven Ellen Dilissen Ingemar von Ossowski Airi Palva Dominique M. Bullens Jos Vanderleyden Sarah Lebeer 《Applied and environmental microbiology》2015,81(6):2050-2062
Recently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG were identified to be key molecules for binding to human intestinal mucus and Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA pilus of L. rhamnosus GG in the interaction with macrophages in vitro by comparing the wild type with surface mutants. Our results show that SpaCBA pili play a significant role in the capacity for adhesion to macrophages and also promote bacterial uptake by these phagocytic cells. Interestingly, our data suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects indirectly by promoting close contact with the macrophages, facilitating the exertion of anti-inflammatory effects by other surface molecules via yet unknown mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be a receptor for streptococcal pili, significantly decreased the uptake of pilus-expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6 mRNA by these macrophages was not affected by this blocking. On the other hand, blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of IL-6 mRNA irrespective of the presence of pili. 相似文献
65.
Ohlsson C Wallaschofski H Lunetta KL Stolk L Perry JR Koster A Petersen AK Eriksson J Lehtimäki T Huhtaniemi IT Hammond GL Maggio M Coviello AD;EMAS Study Group Ferrucci L Heier M Hofman A Holliday KL Jansson JO Kähönen M Karasik D Karlsson MK Kiel DP Liu Y Ljunggren O Lorentzon M Lyytikäinen LP Meitinger T Mellström D Melzer D Miljkovic I Nauck M Nilsson M Penninx B Pye SR Vasan RS Reincke M Rivadeneira F Tajar A Teumer A Uitterlinden AG Ulloor J Viikari J Völker U Völzke H Wichmann HE Wu TS 《PLoS genetics》2011,7(10):e1002313
Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone''s high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG''s affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. 相似文献
66.
Wiederkehr A Szanda G Akhmedov D Mataki C Heizmann CW Schoonjans K Pozzan T Spät A Wollheim CB 《Cell metabolism》2011,13(5):601-611
Mitochondrial Ca(2+) signals have been proposed to accelerate oxidative metabolism and ATP production to match Ca(2+)-activated energy-consuming processes. Efforts to understand the signaling role of mitochondrial Ca(2+) have been hampered by the inability to manipulate matrix Ca(2+) without directly altering cytosolic Ca(2+). We were able to selectively buffer mitochondrial Ca(2+) rises by targeting the Ca(2+)-binding protein S100G to the matrix. We find that matrix Ca(2+) controls signal-dependent NAD(P)H formation, respiration, and ATP changes in intact cells. Furthermore, we demonstrate that matrix Ca(2+) increases are necessary for the amplification of sustained glucose-dependent insulin secretion in β cells. Through the regulation of NAD(P)H in adrenal glomerulosa cells, matrix Ca(2+) also acts as a positive signal in reductive biosynthesis, which stimulates aldosterone secretion. Our dissection of cytosolic and mitochondrial Ca(2+) signals reveals the physiological importance of matrix Ca(2+) in energy metabolism required for signal-dependent hormone secretion. 相似文献
67.
68.
Windahl SH Andersson N Börjesson AE Swanson C Svensson J Movérare-Skrtic S Sjögren K Shao R Lagerquist MK Ohlsson C 《PloS one》2011,6(6):e21402
Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1−/− mice. Four-month-old male Srd5a1
−/− mice had reduced trabecular bone mineral density (−36%, p<0.05) and cortical bone mineral content (−15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1
−/− mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1
−/− mice. Male Srd5a1
−/− mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1
−/− mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1
−/− mice, is an indirect effect mediated by elevated circulating androgen levels. 相似文献
69.
70.