全文获取类型
收费全文 | 717篇 |
免费 | 38篇 |
专业分类
755篇 |
出版年
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 11篇 |
2015年 | 30篇 |
2014年 | 27篇 |
2013年 | 69篇 |
2012年 | 41篇 |
2011年 | 39篇 |
2010年 | 26篇 |
2009年 | 23篇 |
2008年 | 39篇 |
2007年 | 43篇 |
2006年 | 45篇 |
2005年 | 33篇 |
2004年 | 37篇 |
2003年 | 41篇 |
2002年 | 36篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 8篇 |
1997年 | 14篇 |
1996年 | 6篇 |
1995年 | 14篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1969年 | 3篇 |
1967年 | 4篇 |
排序方式: 共有755条查询结果,搜索用时 15 毫秒
61.
62.
Thomaseth K Pavan A Pacini G Ahrén B 《American journal of physiology. Endocrinology and metabolism》2007,292(6):E1808-E1814
Glucagon-like peptide-1 (GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model parameters were estimated from glucose and insulin data collected in 209 anesthetized normal mice after intravenous injection of glucose (1 g/kg) alone or with GLP-1 (0.03-100 nmol/kg). Insulin secretion markedly increased, as expected, with increasing GLP-1 dose. However, minimal model-derived indexes, i.e., insulin sensitivity and glucose effectiveness, did not significantly change with GLP-1 dose. Instead, fractional turnover rate of insulin action [P2 = 0.0207 +/- 24.3% (min) at zero GLP-1 dose] increased steadily with administered GLP-1 dose, with significant differences at 10.4 nmol/kg (P2 = 0.040 +/- 15.5%, P = 0.0046) and 31.2 nmol/kg (P2 = 0.050 +/- 29.2%, P = 0.01). These results show that GLP-1 influences the dynamics of insulin action by accelerating insulin action following glucose challenge. This is a novel mechanism contributing to the glucose-lowering action of GLP-1. 相似文献
63.
64.
Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas 总被引:11,自引:0,他引:11
Bottoni A Zatelli MC Ferracin M Tagliati F Piccin D Vignali C Calin GA Negrini M Croce CM Degli Uberti EC 《Journal of cellular physiology》2007,210(2):370-377
MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by targeting mRNA. It has been demonstrated that miRNA expression is altered in many human cancers, suggesting that they may play a role in human neoplasia. To determine whether miRNA expression is altered in pituitary adenomas, we analyzed the entire miRNAome in 32 pituitary adenomas and in 6 normal pituitary samples by microarray and by Real-Time PCR. Here, we show that 30 miRNAs are differentially expressed between normal pituitary and pituitary adenomas. Moreover, 24 miRNAs were identified as a predictive signature of pituitary adenoma and 29 miRNAs were able to predict pituitary adenoma histotype. miRNA expression could differentiate micro- from macro-adenomas and treated from non-treated patient samples. Several of the identified miRNAs are involved in cell proliferation and apoptosis, suggesting that their deregulated expression may be involved in pituitary tumorigenesis. Predictive miRNAs could be potentially useful diagnostic markers, improving the classification of pituitary adenomas. 相似文献
65.
Impedance spectroscopy has been proposed as possible approach for non-invasive glycaemia monitoring. However, few quantitative data are reported about impedance variations related to glucose concentration variations, especially below the MHz band. Furthermore, it is not clear whether glucose directly affects the impedance parameters or only indirectly by inducing biochemical phenomena. We investigated the impedance variations in glucose-water, glucose-sodium chloride, and glucose-blood samples, for increasing glucose values (up to 300 mg/dl). In all the frequency range (0.1-10(7) Hz) glucose-water samples showed impedance modulus increases for increasing glucose values (up to 135%). In blood and sodium chloride samples the impedance modulus showed only slight variations (2% and 1.4%), but again in wide frequency ranges. Therefore: i) glucose directly affects the impedance parameters of solutions; ii) effects are more relevant at frequencies below the MHz band; iii) the influence on the impedance is decreased in high conductivity solutions, but still clearly present. 相似文献
66.
67.
Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: application to adaptor protein complexes in cell signaling 下载免费PDF全文
Houtman JC Brown PH Bowden B Yamaguchi H Appella E Samelson LE Schuck P 《Protein science : a publication of the Protein Society》2007,16(1):30-42
Multisite interactions and the formation of ternary or higher-order protein complexes are ubiquitous features of protein interactions. Cooperativity between different ligands is a hallmark for information transfer, and is frequently critical for the biological function. We describe a new computational platform for the global analysis of isothermal titration calorimetry (ITC) data for the study of binary and ternary multisite interactions, implemented as part of the public domain multimethod analysis software SEDPHAT. The global analysis of titrations performed in different orientations was explored, and the potential for unraveling cooperativity parameters in multisite interactions was assessed in theory and experiment. To demonstrate the practical potential and limitations of global analyses of ITC titrations for the study of cooperative multiprotein interactions, we have examined the interactions of three proteins that are critical for signal transduction after T-cell activation, LAT, Grb2, and Sos1. We have shown previously that multivalent interactions between these three molecules promote the assembly of large multiprotein complexes important for T-cell receptor activation. By global analysis of the heats of binding observed in sets of ITC injections in different orientations, which allowed us to follow the formation of binary and ternary complexes, we observed negative and positive cooperativity that may be important to control the pathway of assembly and disassembly of adaptor protein particles. 相似文献
68.
IGF-1 system, Vitamin D and blood pressure relationships 总被引:1,自引:0,他引:1
69.
Bontempo P Mita L Miceli M Doto A Nebbioso A De Bellis F Conte M Minichiello A Manzo F Carafa V Basile A Rigano D Sorbo S Castaldo Cobianchi R Schiavone EM Ferrara F De Simone M Vietri M Cioffi M Sica V Bresciani F de Lera AR Altucci L Molinari AM 《The international journal of biochemistry & cell biology》2007,39(10):1902-1914
Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems. 相似文献
70.
Biscotti MA Canapa A Olmo E Barucca M Teo CH Schwarzacher T Dennerlein S Richter R Heslop-Harrison JS 《Gene》2007,406(1-2):91-98
We studied the structure, organization and relationship of repetitive DNA sequences in the genome of the scallop, Pecten maximus, a bivalve that is important both commercially and in marine ecology. Recombinant DNA libraries were constructed after partial digestion of genomic DNA from scallop with PstI and ApaI restriction enzymes. Clones containing repetitive DNA were selected by hybridisation to labelled DNA from scallop, oyster and mussel; colonies showing strong hybridisation only to scallop were selected for analysis and sequencing. Six non-homologous tandemly repeated sequences were identified in the sequences, and Southern hybridisation with all repeat families to genomic DNA digests showed characteristic ladders of hybridised bands. Three families had monomer lengths around 40 bp while three had repeats characteristic of the length wrapping around one (170 bp), or two (326 bp) nucleosomes. In situ hybridisation to interphase nuclei showed each family had characteristic numbers of clusters indicating contrasting arrangements. Two of the repeats had unusual repetitions of bases within their sequence, which may relate to the nature of microsatellites reported in bivalves. The study of these rapidly evolving sequences is valuable to understand an important source of genomic diversity, has the potential to provide useful markers for population studies and gives a route to identify mechanisms of DNA sequence evolution. 相似文献