全文获取类型
收费全文 | 1406篇 |
免费 | 131篇 |
出版年
2023年 | 9篇 |
2022年 | 10篇 |
2021年 | 53篇 |
2020年 | 31篇 |
2019年 | 36篇 |
2018年 | 33篇 |
2017年 | 35篇 |
2016年 | 43篇 |
2015年 | 78篇 |
2014年 | 84篇 |
2013年 | 79篇 |
2012年 | 129篇 |
2011年 | 92篇 |
2010年 | 64篇 |
2009年 | 55篇 |
2008年 | 69篇 |
2007年 | 70篇 |
2006年 | 48篇 |
2005年 | 50篇 |
2004年 | 52篇 |
2003年 | 50篇 |
2002年 | 45篇 |
2001年 | 18篇 |
2000年 | 19篇 |
1999年 | 16篇 |
1998年 | 8篇 |
1997年 | 11篇 |
1996年 | 22篇 |
1995年 | 18篇 |
1994年 | 9篇 |
1993年 | 16篇 |
1992年 | 9篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 14篇 |
1986年 | 9篇 |
1985年 | 6篇 |
1983年 | 8篇 |
1979年 | 6篇 |
1977年 | 5篇 |
1973年 | 5篇 |
1972年 | 7篇 |
1969年 | 6篇 |
1968年 | 4篇 |
1929年 | 4篇 |
1918年 | 4篇 |
1912年 | 4篇 |
1911年 | 10篇 |
1910年 | 6篇 |
排序方式: 共有1537条查询结果,搜索用时 46 毫秒
91.
92.
One of the great strengths of the Framingham Heart Study data, provided for the Genetic Analysis Workshop 13, is the long-term survey of phenotypic data. We used this unique data to create new phenotypes representing the pattern of longitudinal change of the provided phenotypes, especially systolic blood pressure and body weight. We performed a linear regression of body weight and systolic blood pressure on age and took the slopes as new phenotypes for quantitative trait linkage analysis using the SOLAR package. There was no evidence for heritability of systolic blood pressure change. Heritability was estimated as 0.15 for adult life "body weight change", measured as the regression slope, and "body weight gain" (including only individuals with a positive regression slope), and as 0.22 for body weight "change up to 50" (regression slope of weight on age up to an age of 50). With multipoint analysis, two regions on the long arm of chromosome 8 showed the highest LOD scores of 1.6 at 152 cM for "body weight change" and of >1.9 around location 102 cM for "body weight gain" and "change up to 50". The latter two LOD scores almost reach the threshold for suggestive linkage. We conclude that the chromosome 8 region may harbor a gene acting on long-term body weight regulation, thereby contributing to the development of the metabolic syndrome. 相似文献
93.
Ethanol oxidation by nicotinoprotein alcohol dehydrogenase (np-ADH) from the bacterium Amycolatopsis methanolica is inhibited by trans-4-(N,N-dimethylamino)-cinnamaldehyde through direct binding to the catalytic zinc ion in a substrate-like geometry. This binding is accompanied by a characteristic red shift of the aldehyde absorbance from 398 nm to 467 nm. Np-ADH is structurally related to mammalian ADH class I, and a model of np-ADH shows how the cinnamaldehyde derivative can be accommodated in the active site of the nicotinoprotein, correlating the structural and enzymological data. 相似文献
94.
95.
Epithelial-mesenchymal transformation is the mechanism for fusion of the craniofacial primordia involved in morphogenesis of the chicken lip 总被引:3,自引:0,他引:3
We have previously demonstrated that epithelial-mesenchymal transformation (EMT) brings about TGF beta 3-induced confluence of craniofacial primordia that derive from the maxillary processes and give rise to the avian palate. The upper lip of the chick embryo forms by confluence of primordia also derived from the maxillary processes, but in this case, they fuse with the intermaxillary segment of the nasofrontal process. Here, we ask whether the bilateral epithelial seams formed when these primordia contact each other in vivo are removed by apoptosis (as formerly was believed to occur in developing palate) or by EMT. We found that, as is the case in the palate, the periderm of the two-layered embryonic epithelium begins to slough shortly before these primordia fuse, bringing the basal epithelial cells into close contact. We show by TUNEL staining and confirm by TEM that apoptosis occurs only in periderm. TEM reveals that basal epithelial cells contacting each other to form the midline seam produce numerous desmosomes with each other. Then, basement membrane begins to disappear, numerous filopodia extend from the basal surfaces of epithelial cells, the space between them enlarges, and the seam breaks apart, leaving mesenchymal cells in its wake. Transformation of the carboxyfluorescein (CCFSE)-labeled epithelial seam is demonstrated in vivo by detection of CCFSE bodies in mesenchymal cells that replace it. This demonstration of EMT in avian lip development lays important groundwork for understanding the causes of human cleft lip and analyzing the mechanism of action of growth factors, such as SHH and BMPs, that have been shown (J. A. Helms et al., 1997, Dev. Biol. 187, 25-35) to be involved in avian lip confluence. 相似文献
96.
In the preceding paper [B. Marczynski, P. Rozynek, T. Kraus, St. Schl?sser, H.J. Raithel, X. Baur, Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers highly exposed to asbestos in Germany, Mutat. Res. (2000) submitted] we described significant increases (p<0.001) in the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells (WBC) of workers highly exposed to asbestos fibers at the workplace relative to those found in the control group in all three study years (period between 1994 and 1997). The results show that the oxidative DNA damage in exposed individuals is between 1.7 times and twice that found in control samples for all 3 years of the study (p<0.001). The aim of this study was to examine the association between the 8-OHdG levels in WBC DNA of workers highly exposed to asbestos fibers at the workplace and clinical data, occupational and non-occupational confounding factors, and cancer. There is no obvious correlation between the steady-state levels of 8-OHdG in the circulating WBC DNA of asbestos workers and possible confounding factors, such as the presence of benign asbestos-associated diseases, the duration of asbestos exposure, the latency period, the fixed cumulative fibrous dust dose ("fiber years"), age, smoking status, acute febrile infections, medicines, aspirin, calcium (Ca(2+)), magnesium (Mg(2+)), and the hormone and vitamin intake. This indicates that previous inhalation of asbestos fibers is the major factor responsible for the difference observed in oxidative DNA damage between asbestos workers and controls. For patients suffering from respiratory cancer, cancer of the gastrointestinal tract, mouth/pharynx/larynx, and urogenital tract the mean DNA-adduct level was significantly higher (p<0.01) than that found in controls, but not significantly higher (p>0.05) than that for asbestos-exposed patients without tumours. The formation of 8-OHdG adduct levels in WBC DNA of patients with hematopoietic cancer, chondrosarcomas and multiform glioblastomas was not significantly higher than that found in the control group (p>0.05). Our results support the hypothesis that oxidative DNA damage in man caused by asbestos fibers plays a role in the formation of malignant tumours. 相似文献
97.
Mats W. Levall Karina Bengtsson Nils-Otto Nilsson Annika Hjerdin Christer Halldén 《Physiologia plantarum》1994,90(1):216-220
Sugar beet plants regenerated from UV-treated calluses were examined by restriction fragment length polymorphism (RFLP) analysis to determine the extent of somaclonal variation occurring at the DNA level. In total, 50 random sugar beet DNA sequences were used to screen 42 somaclones for genetic alterations. Three polymorphisms were detected among the 7 644 alleles analysed. From these data a mutation frequency of 0.03 ± 0.02% per allele was estimated. This frequency is in agreement with similar studies of somaclonal DNA variation using molecular markers and lies in the upper range of the spontaneous gene mutation frequencies found in plants. The two probegenotype combinations showing independent polymorphisms, were further analysed using the restriction enzymes Bam HI, Eco RI, Eco RV and Hind III. Both polymorphisms are likely to result from structural rearrangements rather than from point mutations. Differences in methylation among 10 of the investigated somaclones were tested for by comparing Hpa II and Msp I generated RFLP patterns. The somaclones showed extensive methylation, but no differences in their degree of methylation. Cytological analysis revealed 34 diploid, 8 tetraploid, but no aneuploid plants. 相似文献
98.
99.
Lydia Herrmann Caspar Wiegmann Annika Arsalan-Werner Isabel Hilbrich Carsten J?ger Katharina Flach Anne Suttkus Ingolf Lachmann Thomas Arendt Max Holzer 《PloS one》2015,10(3)
Defects in intracellular transport are implicated in the pathogenesis of Alzheimer’s disease (AD). Hook proteins are a family of cytoplasmic linker proteins that participate in endosomal transport. In this study we show that Hook1 and Hook3 are expressed in neurons while Hook2 is predominantly expressed in astrocytes. Furthermore, Hook proteins are associated with pathological hallmarks in AD; Hook1 and Hook3 are localized to tau aggregates and Hook2 to glial components within amyloid plaques. Additionally, the expression of Hook3 is reduced in AD. Modelling of Hook3 deficiency in cultured cells leads to slowing of endosomal transport and increases β-amyloid production. We propose that Hook3 plays a role in pathogenic events exacerbating AD. 相似文献
100.
Lena Bj?rck Simon Capewell Martin O’Flaherty Georgios Lappas Kathleen Bennett Annika Rosengren 《PloS one》2015,10(5)
BackgroundThe relative importance of risk factor reduction in healthy people (primary prevention) versus that in patients with coronary heart disease (secondary prevention) has been debated. We aimed to quantify the contribution of the two.MethodologyWe used the previously validated IMPACT model to estimate contributions from primary prevention (reducing risk factors in the population, particularly smoking, cholesterol and systolic blood pressure) and from secondary prevention (reducing risk factors in coronary heart disease patients) in the Swedish population.ConclusionsThe largest effects on mortality came from primary prevention, giving markedly larger mortality reductions than secondary prevention. 相似文献