全文获取类型
收费全文 | 349篇 |
免费 | 28篇 |
出版年
2022年 | 3篇 |
2018年 | 3篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 10篇 |
2013年 | 22篇 |
2012年 | 14篇 |
2011年 | 17篇 |
2010年 | 7篇 |
2009年 | 11篇 |
2008年 | 16篇 |
2007年 | 15篇 |
2006年 | 11篇 |
2005年 | 12篇 |
2004年 | 13篇 |
2003年 | 12篇 |
2002年 | 7篇 |
2001年 | 15篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1974年 | 5篇 |
1972年 | 6篇 |
1969年 | 3篇 |
1966年 | 4篇 |
1955年 | 2篇 |
1954年 | 2篇 |
1935年 | 2篇 |
1924年 | 2篇 |
排序方式: 共有377条查询结果,搜索用时 15 毫秒
31.
Lanningham-Foster L Green CL Langkamp-Henken B Davis BA Nguyen KT Bender BS Cousins RJ 《American journal of physiology. Endocrinology and metabolism》2002,282(6):E1197-E1203
Cysteine-rich intestinal protein (CRIP), which contains a double zinc finger motif, is a member of the Group 2 LIM protein family. Our results showed that the developmental regulation of CRIP in neonates was not influenced by conventional vs. specific pathogen-free housing conditions. Thymic and splenic CRIP expression was not developmentally regulated. A line of transgenic (Tg) mice that overexpress the rat CRIP gene was created. When challenged with lipopolysaccharide, the Tg mice lost more weight, exhibited increased mortality, experienced greater diarrhea incidence, and had less serum interferon-gamma (IFN-gamma) and more interleukin (IL)-6 and IL-10. Similarly, splenocytes from the Tg mice produced less IFN-gamma and IL-2 and more IL-10 and IL-6 upon mitogen stimulation. Delayed-type hypersensitivity response was less in the Tg mice. Influenza virus infection produced greater weight loss in the Tg mice, which also showed delayed viral clearance. The observed responses to overexpression of the CRIP gene are consistent with a role for this LIM protein in a cellular pathway that produces an imbalance in cytokine pattern favoring Th2 cytokines. 相似文献
32.
33.
Herrmann PC Gillespie JW Charboneau L Bichsel VE Paweletz CP Calvert VS Kohn EC Emmert-Buck MR Liotta LA Petricoin EF 《Proteomics》2003,3(9):1801-1810
Laser capture microdissection was combined with reverse phase protein lysate arrays to quantitatively analyze the ratios of mitochondrial encoded cytochrome c oxidase subunits to nuclear encoded cytochrome c oxidase subunits, and to correlate the ratios with malignant progression in human prostate tissue specimens. Cytochrome c oxidase subunits I-III comprise the catalytic core of the enzyme and are all synthesized from mitochondrial DNA. The remaining subunits (IV-VIII) are synthesized from cellular nuclear DNA. A significant (P < 0.001, 30/30 prostate cases) shift in the relative concentrations of nuclear encoded cytochrome c oxidase subunits IV, Vb, and VIc compared to mitochondrial encoded cytochrome c oxidase subunits I and II was noted during the progression of prostate cancer from normal epithelium through premalignant lesions to invasive carcinoma. Significantly, this shift was discovered to begin even in the premalignant stage. Reverse phase protein lysate array-based observations were corroborated with immunohistochemistry, and extended to a few human carcinomas in addition to prostate. This analysis points to a role for nuclear DNA encoded mitochondrial proteins in carcinogenesis; underscoring their potential as targets for therapy while highlighting the need for full characterization of the mitochondrial proteome. 相似文献
34.
Calvert MJ Ward DG Trayer HR Trayer IP 《The Journal of biological chemistry》2000,275(42):32508-32515
The interactions between troponin I and troponin C are central to the Ca(2+)-regulated control of striated muscle. Using isothermal titration microcalorimetry we have studied the binding of human cardiac troponin C (cTnC) and its isolated domains to human cardiac troponin I (cTnI). We provide the first binding data for these proteins while they are free in solution and unmodified by reporter groups. Our data reveal that the C-terminal domain of cTnC is responsible for most of the free energy change upon cTnC.cTnI binding. Importantly, the interaction between cTnI and the C-terminal domain of cTnC is 8-fold stronger in the presence of Ca(2+) than in the presence of Mg(2+), suggesting that the C-terminal domain of cTnC may play a modulatory role in cardiac muscle regulation. Changes in the affinity of cTnI for cTnC and its isolated C-terminal domain in response to ionic strength support this finding, with both following similar trends. At physiological ionic strength the affinity of cTnC for cTnI changed very little in response to Ca(2+), although the thermodynamic data show a clear distinction between binding in the presence of Ca(2+) and in the presence of Mg(2+). 相似文献
35.
In vivo DNA damage in gastric epithelial cells 总被引:6,自引:0,他引:6
Everett SM White KL Schorah CJ Calvert RJ Skinner C Miller D Axon AT 《Mutation research》2000,468(1):73-85
A number of risk factors have been linked epidemiologically with gastric cancer, but studies of DNA damage in gastric epithelial cells are limited. The comet assay is a simple technique for determining levels of DNA damage in individual cells. In this study, we have validated the comet assay for use in epithelial cells derived directly from human gastric biopsies, determined optimal conditions for biopsy digestion and investigated the effects of oxidative stress and digestion time on DNA damage. Biopsies taken at endoscopy were digested using combinations of pronase and collagenase, ethylenediaminetetra-acetic acid (EDTA) and vigorous shaking. The resultant cell suspension was assessed for cell concentration and epithelial cell and leukocyte content. A score for DNA damage, the comet %, was derived from the cell suspension, and the effect of various digestion conditions was studied. Cells were incubated with H(2)O(2) and DNA damage was assessed. Pronase and collagenase provided optimum digestion conditions, releasing 1. 12x10(5) cells per biopsy, predominantly epithelial. Of the 23 suspensions examined, all but three had leukocyte concentrations of less than 20%. The comet assay had high inter-observer (6.1%) and inter-assay (4.5%) reproducibility. Overnight storage of the biopsy at 4 degrees C had no significant effect on DNA migration. Comet % increased from a median of 46% in untreated cells to 88% in cells incubated for 45 min in H(2)O(2) (p=0.005). Serial 25-min digestions were performed on biopsies from 13 patients to release cells from successively deeper levels in the crypt. Levels of DNA migration were significantly lower with each digestion (r=-0.94, p<0.001), suggesting that DNA damage is lower in younger cells released from low in the gastric crypt. The comet assay is a reproducible measure of DNA damage in gastric epithelial cells. Damage accumulates in older, more superficial cells, and can be induced by oxidative stress. 相似文献
36.
Parasitic worms survive within their immunocompetent hosts by modulating their immune system and by inhibiting inflammatory responses directed against the parasites. This immunomodulation has a spill over effect and also inhibits inflammatory responses originating from other causes. For this reason, persons who are infected with certain species of worms show a lower rate of allergic diseases as compared to persons who are free of parasites. In the same line, studies in mouse models revealed that many inflammatory diseases can be treated by worm infections. This effect is among others owing to specific proteins that are released by the worms. Such secreted immunomodulators, shaped by co‐evolution between parasites and their hosts, could become lead compounds for the development of new therapies against allergic and inflammatory diseases. 相似文献
37.
Hong Zhu Hee Yun Suk Raymond Y. L. Yu Deborah Brancho Opeyemi Olabisi Teddy T. C. Yang XiaoYong Yang Jialin Zhang Mustapha Moussaif Jorge L. Durand Linda A. Jelicks Ja-Young Kim Philipp E. Scherer Philippe G. Frank Michael P. Lisanti John W. Calvert Mark R. Duranski David J. Lefer Elaine Huston George S. Baillie Miles D. Houslay Jeffrey D. Molkentin Jianping Jin Chi-Wing Chow 《Molecular and cellular biology》2010,30(18):4379-4390
38.
PD Dr. N. Wolf 《Medizinische Genetik》2007,19(4):414-417
Dental anomalies in children with neuropediatric disorders are easy to diagnose and can be essential in the diagnosis of different entities. They are present in well-known disorders as Incontinentia pigmenti, but also in rare diseases as in Kohlschütter-Tönz syndrome or the recently described ataxia, delayed dentition and hypomyelination. Anomalies of dental shape, enamel and in this case also teeth color, dental number and eruption are all encountered. Knowledge of these abnormalities is important for both clinical geneticist and child neurologist. 相似文献
39.
Because of their high prevalence, cases of coronary artery disease (CAD) and myocardial infarction (MI) are frequently found when asking for a patient’s family history. It is common knowledge that a positive familial history constitutes a risk factor for CAD in its own right, in addition to smoking, increased alcohol intake, diabetes, obesity, hypertension, and hyperlipidemia. Nevertheless, for correct risk assessment it is crucial to accurately distinguish between sporadic and true familial cases of CAD and MI. Familial disposition is present when at least one male first-grade relative under the age of 55 or one female first-grade relative under the age of 65 has/had been diagnosed with myocardial infarction or significant coronary artery disease. In the review presented here, we compile the relevant epidemiological and genetic studies that constitute the scientific basis of this risk assessment. Furthermore, a short overview of the state of the art of genetic CAD/MI research is given. 相似文献