全文获取类型
收费全文 | 8271篇 |
免费 | 780篇 |
国内免费 | 2篇 |
专业分类
9053篇 |
出版年
2024年 | 4篇 |
2023年 | 42篇 |
2022年 | 84篇 |
2021年 | 184篇 |
2020年 | 120篇 |
2019年 | 138篇 |
2018年 | 175篇 |
2017年 | 180篇 |
2016年 | 231篇 |
2015年 | 430篇 |
2014年 | 477篇 |
2013年 | 606篇 |
2012年 | 747篇 |
2011年 | 719篇 |
2010年 | 450篇 |
2009年 | 421篇 |
2008年 | 589篇 |
2007年 | 518篇 |
2006年 | 505篇 |
2005年 | 458篇 |
2004年 | 476篇 |
2003年 | 351篇 |
2002年 | 383篇 |
2001年 | 100篇 |
2000年 | 67篇 |
1999年 | 85篇 |
1998年 | 90篇 |
1997年 | 58篇 |
1996年 | 34篇 |
1995年 | 35篇 |
1994年 | 27篇 |
1993年 | 36篇 |
1992年 | 21篇 |
1991年 | 23篇 |
1990年 | 25篇 |
1989年 | 18篇 |
1988年 | 12篇 |
1987年 | 14篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 14篇 |
1983年 | 9篇 |
1982年 | 13篇 |
1981年 | 8篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1973年 | 4篇 |
1972年 | 6篇 |
1960年 | 3篇 |
排序方式: 共有9053条查询结果,搜索用时 0 毫秒
21.
One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure.Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders. 相似文献
22.
23.
24.
Matthias Wurm An-Ping Zeng 《Metabolomics : Official journal of the Metabolomic Society》2012,8(6):1081-1089
The quantification of metabolite leakage from damaged mammalian cells to the surrounding medium is of high interest for the processing of samples for metabolomic analysis. It is also of relevance to know the typical time span which is required for a promoted metabolite release through a selectively permeabilized cell membrane. The real-time observation of such a process is difficult since small metabolites cannot be observed directly by optical methods and other more indirect assays can disturb the metabolite concentration itself. However, the diffusion based loss of metabolites from the cytoplasm can be predicted on the basis of reference measurements taken from an easy-to-detect molecule with known diffusion coefficient. In this work, we use green fluorescent protein (GFP) as a marker and model its release from damaged cells using the finite-element method. A correlation between the disrupted membrane area fraction, A d , the distribution of membrane ruptures and the rate of GFP efflux, k e , has been established. k e has been determined experimentally for Chinese hamster ovary cells, which have been damaged mechanically by passage through a micronozzle geometry in a microfluidic system. The immediate GFP release downstream of the micronozzles has been observed in real-time and the corresponding membrane damage has been predicted. On this basis, we calculated the expected times required for the drainage of freely diffusable cytosolic glucose and found a loss of ??90% within 1 s for a disrupted membrane area fraction of ??5%. Hence, even minimal membrane damage would lead to a rapid loss of cytosolic metabolites by diffusion unless membrane resealing processes take place. 相似文献
25.
26.
Mohammad Abdel-Halim Adam B. Keeton Evrim Gurpinar Bernard D. Gary Simon M. Vogel Matthias Engel Gary A. Piazza Frank M. Boeckler Rolf W. Hartmann Ashraf H. Abadi 《Bioorganic & medicinal chemistry》2013,21(23):7343-7356
Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra-substituted pyrazoline were synthesized and tested for their inhibitory effects versus the p53+/+ HCT116 and p53?/? H1299 human tumor cell lines. Several compounds were active against the two cell lines displaying IC50 values in the low micromolar range with a clearly more pronounced effect on the p53+/+ HCT116 cells. The compound class shows excellent developability due to the modular synthesis, allowing independent optimization of all three to four key substituents to improve the properties of the molecules. 相似文献
27.
Lisa N. Meihls Vinzenz Handrick Gaetan Glauser Hugues Barbier Harleen Kaur Meena M. Haribal Alexander E. Lipka Jonathan Gershenzon Edward S. Buckler Matthias Erb Tobias G. K?llner Georg Jander 《The Plant cell》2013,25(6):2341-2355
Plants differ greatly in their susceptibility to insect herbivory, suggesting both local adaptation and resistance tradeoffs. We used maize (Zea mays) recombinant inbred lines to map a quantitative trait locus (QTL) for the maize leaf aphid (Rhopalosiphum maidis) susceptibility to maize Chromosome 1. Phytochemical analysis revealed that the same locus was also associated with high levels of 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside (HDMBOA-Glc) and low levels of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one glucoside (DIMBOA-Glc). In vitro enzyme assays with candidate genes from the region of the QTL identified three O-methyltransferases (Bx10a-c) that convert DIMBOA-Glc to HDMBOA-Glc. Variation in HDMBOA-Glc production was attributed to a natural CACTA family transposon insertion that inactivates Bx10c in maize lines with low HDMBOA-Glc accumulation. When tested with a population of 26 diverse maize inbred lines, R. maidis produced more progeny on those with high HDMBOA-Glc and low DIMBOA-Glc. Although HDMBOA-Glc was more toxic to R. maidis than DIMBOA-Glc in vitro, BX10c activity and the resulting decline of DIMBOA-Glc upon methylation to HDMBOA-Glc were associated with reduced callose deposition as an aphid defense response in vivo. Thus, a natural transposon insertion appears to mediate an ecologically relevant trade-off between the direct toxicity and defense-inducing properties of maize benzoxazinoids. 相似文献
28.
Hye Jin Yoo Soon Young Hwang Ho Cheol Hong Hae Yoon Choi Sae Jeong Yang Dong Seop Choi Sei Hyun Baik Matthias Blüher Byung-Soo Youn Kyung Mook Choi 《PloS one》2013,8(2)
Objective
Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance.Research Design and Methods
We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT).Results
Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = −0.21), diastolic blood pressure (r = −0.21), fasting glucose (r = −0.20), triglyceride (r = −0.34), total cholesterol (r = −0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R 2 = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R 2 = 0.365).Conclusions
Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome.Trial Registration
ClinicalTrials.gov NCT01668888相似文献29.
Fatemeh Jamali Abbas Sharifi-Tehrani Matthias P. Lutz Monika Maurhofer 《Microbial ecology》2009,57(2):267-275
The production of hydrogen cyanide (HCN) and 2,4-diacetylphloroglucinol (DAPG) is a major factor in the control of soil-borne
diseases by Pseudomonas fluorescens CHA0. We investigated the impact of different biotic factors on the expression of HCN–in comparison to DAPG biosynthetic
genes in the rhizosphere. To this end, the influence of plant cultivar, pathogen infection, and coinoculation with other biocontrol
strains on the expression of hcnA-lacZ and phlA-lacZ fusion in strain CHA0 was monitored on the roots of bean. Interestingly, all the tested factors influenced the expression
of the two biocontrol traits in a similar way. For both genes, we observed a several-fold higher expression in the rhizosphere
of cv. Derakhshan compared with cvs. Goli and Naz, although bacterial rhizosphere colonization levels were similar on all
cultivars tested. Root infection by Rhizoctonia solani stimulated total phlA and hcnA gene expression in the bean rhizosphere. Coinoculation of strain CHA0 with DAPG-producing P. fluorescens biocontrol strains Pf-68 and Pf-100 did neither result in a substantial alteration of hcnA nor of phlA expression in CHA0 on bean roots. To our best knowledge, this is the first study investigating the impact of biotic factors
on HCN production by a bacterial biocontrol strain in the rhizosphere. 相似文献
30.