全文获取类型
收费全文 | 657篇 |
免费 | 43篇 |
专业分类
700篇 |
出版年
2023年 | 4篇 |
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 18篇 |
2015年 | 18篇 |
2014年 | 26篇 |
2013年 | 30篇 |
2012年 | 43篇 |
2011年 | 32篇 |
2010年 | 14篇 |
2009年 | 24篇 |
2008年 | 21篇 |
2007年 | 22篇 |
2006年 | 20篇 |
2005年 | 18篇 |
2004年 | 27篇 |
2003年 | 31篇 |
2002年 | 25篇 |
2001年 | 23篇 |
2000年 | 21篇 |
1999年 | 21篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 13篇 |
1987年 | 16篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1984年 | 14篇 |
1983年 | 5篇 |
1981年 | 7篇 |
1979年 | 9篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1972年 | 5篇 |
1971年 | 5篇 |
1970年 | 3篇 |
1966年 | 4篇 |
1965年 | 5篇 |
排序方式: 共有700条查询结果,搜索用时 0 毫秒
71.
Hennig H Fleischmann R Fredebohm A Hagmayer Y Nagler J Witt A Theis FJ Geisel T 《PloS one》2011,6(10):e26457
Although human musical performances represent one of the most valuable achievements of mankind, the best musicians perform imperfectly. Musical rhythms are not entirely accurate and thus inevitably deviate from the ideal beat pattern. Nevertheless, computer generated perfect beat patterns are frequently devalued by listeners due to a perceived lack of human touch. Professional audio editing software therefore offers a humanizing feature which artificially generates rhythmic fluctuations. However, the built-in humanizing units are essentially random number generators producing only simple uncorrelated fluctuations. Here, for the first time, we establish long-range fluctuations as an inevitable natural companion of both simple and complex human rhythmic performances. Moreover, we demonstrate that listeners strongly prefer long-range correlated fluctuations in musical rhythms. Thus, the favorable fluctuation type for humanizing interbeat intervals coincides with the one generically inherent in human musical performances. 相似文献
72.
Anne Gulbech Ording Jens Peter Garne Petra Mariann Witt Nystr?m Deirdre Cronin-Fenton Maja Tarp Henrik Toft S?rensen Timothy L. Lash 《PloS one》2012,7(10)
Introduction
Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth.Methods
Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods.Results
The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment.Conclusions
There was no substantial association between morbidity measured with the CCI and breast cancer risk. 相似文献73.
74.
75.
Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: evidence consistent with a glycidamide-mediated effect 总被引:8,自引:0,他引:8
Acrylamide, an animal carcinogen and germ cell mutagen present at low (ppm) levels in heated carbohydrate-containing foodstuffs, is oxidized by cytochrome P4502E1 (CYP2E1) to the epoxide glycidamide, which is believed to be responsible for the mutagenic and carcinogenic activity of acrylamide. We recently reported a comparison of the effects of acrylamide on the genetic integrity of germ cells of male wild-type and CYP2E1-null mice [B.I. Ghanayem, K.L. Witt, L. El-Hadri, U. Hoffler, G.E. Kissling, M.D. Shelby, J.B. Bishop, Comparison of germ-cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect, Biol. Reprod. 72 (2005) 157-163]. In those experiments, dose-related increases in dominant lethal mutations were detected in uterine contents of female mice mated to acrylamide-treated wild-type males but not CYP2E1-null males, clearly implicating CYP2E1-mediated formation of glycidamide in the induction of genetic damage in male germ cells. We hypothesized that acrylamide-induced somatic cell damage is also caused by glycidamide. Therefore, to examine this hypothesis, female wild-type and CYP2E1-null mice were administered acrylamide (0, 25, 50mg/kg) by intraperitoneal injection once daily for 5 consecutive days. Twenty-four hours after the final treatment, blood and tissue samples were collected. Erythrocyte micronucleus frequencies were determined using flow cytometry and DNA damage was assessed in leukocytes, liver, and lung using the alkaline (pH>13) single cell gel electrophoresis (Comet) assay. Results were consistent with the earlier observations in male germ cells: significant dose-related increases in micronucleated erythrocytes and DNA damage in somatic cells were induced in acrylamide-treated wild-type but not in the CYP2E1-null mice. These results support the hypothesis that genetic damage in somatic and germ cells of mice-treated with acrylamide is dependent upon metabolism of the parent compound by CYP2E1. This dependency on metabolism has implications for the assessment of human risks resulting from occupational or dietary exposure to acrylamide. CYP2E1 polymorphisms and variability in CYP2E1 activity associated with, for example, diabetes, obesity, starvation, and alcohol consumption, may result in altered metabolic efficiencies leading to differential susceptibilities to acrylamide toxicities in humans. 相似文献
76.
Ghanayem BI Witt KL El-Hadri L Hoffler U Kissling GE Shelby MD Bishop JB 《Biology of reproduction》2005,72(1):157-163
Acrylamide is an animal carcinogen and probable human carcinogen present in appreciable amounts in heated carbohydrate-rich foodstuffs. It is also a germ cell mutagen, inducing dominant lethal mutations and heritable chromosomal translocations in postmeiotic sperm of treated mice. Acrylamide's affinity for male germ cells has sometimes been overlooked in assessing its toxicity and defining human health risks. Previous investigations of acrylamide's germ cell activity in mice showed stronger effects after repeated administration of low doses compared with a single high dose, suggesting the possible involvement of a stable metabolite. A key oxidative metabolite of acrylamide is the epoxide glycidamide, generated by cytochrome P4502E1 (CYP2E1). To explore the role of CYP2E1 metabolism in the germ cell mutagenicity of acrylamide, CYP2E1-null and wild-type male mice were treated by intraperitoneal injection with 0, 12.5, 25, or 50 mg acrylamide (5 ml saline)(-1) kg(-1) day(-1) for 5 consecutive days. At defined times after exposure, males were mated to untreated B6C3F1 females. Females were killed in late gestation and uterine contents were examined. Dose-related increases in resorption moles (chromosomally aberrant embryos) and decreases in the numbers of pregnant females and the proportion of living fetuses were seen in females mated to acrylamide-treated wild-type mice. No changes in any fertility parameters were seen in females mated to acrylamide-treated CYP2E1-null mice. Our results constitute the first unequivocal demonstration that acrylamide-induced germ cell mutations in male mice require CYP2E1-mediated epoxidation of acrylamide. Thus, CYP2E1 polymorphisms in human populations, resulting in variable enzyme metabolic activities, may produce differential susceptibilities to acrylamide toxicities. 相似文献
77.
The insect antimicrobial peptide, L-pyrrhocoricin, binds to and stimulates the ATPase activity of both wild-type and lidless DnaK 总被引:2,自引:0,他引:2
Recent reports have indicated that insect antimicrobial peptides kill bacteria by inhibiting the molecular chaperone DnaK. It was proposed that the antimicrobial peptide, all-L-pyrrhocoricin (L-PYR), binds to two sites on DnaK, the conventional substrate-binding site and the multi-helical C-terminal lid, and that inhibition of DnaK comes about from the lid mode of binding. In this report, we show using two different assays that L-PYR binds to and stimulates the ATPase activity of both wild-type and a lidless variant of DnaK. Our study shows that L-PYR interacts with DnaK much like the all-L NR (NRLLLTG) peptide, which is known to bind in the conventional substrate-binding site of DnaK. L-PYR antimicrobial activity is thus a consequence of the competitive inhibition of bacterial DnaK. 相似文献
78.
The neuronal protein α-synuclein (α-syn) has been suggested to be one of the factors linked to Parkinson's disease (PD). Several organisms, including the rat, mouse, worm, and fruit fly, are being used to study α-syn pathobiology. A new model organism was recently added to this armamentarium: the budding yeast Saccharomyces cerevisiae . The yeast system recapitulates many of the findings made with higher eukaryotes. For example, yeast cells expressing α-syn accumulate lipid droplets, have vacuolar/lysosomal defects, and exhibit markers of apoptosis, including the externalization of phosphatidylserine, the release of cytochrome c , and the accumulation of reactive oxygen species. This MiniReview focuses on the mechanisms by which α-syn induces oxidative stress and the mechanisms by which yeast cells respond to this stress. Three classes of therapeutics are discussed. 相似文献
79.
Witt CC Burkart C Labeit D McNabb M Wu Y Granzier H Labeit S 《The EMBO journal》2006,25(16):3843-3855
The precise assembly of the highly organized filament systems found in muscle is critically important for its function. It has been hypothesized that nebulin, a giant filamentous protein extending along the entire length of the thin filament, provides a blueprint for muscle thin filament assembly. To test this hypothesis, we generated a KO mouse model to investigate nebulin functions in vivo. Nebulin KO mice assemble thin filaments of reduced lengths and approximately 15% of their Z-disks are abnormally wide. Our data demonstrate that nebulin functions in vivo as a molecular ruler by specifying pointed- and barbed-end thin filament capping. Consistent with the shorter thin filament length of nebulin deficient mice, maximal active tension was significantly reduced in KO animals. Phenotypically, the murine model recapitulates human nemaline myopathy (NM), that is, the formation of nemaline rods combined with severe skeletal muscle weakness. The myopathic changes in the nebulin KO model include depressed contractility, loss of myopalladin from the Z-disk, and dysregulation of genes involved in calcium homeostasis and glycogen metabolism; features potentially relevant for understanding human NM. 相似文献
80.