全文获取类型
收费全文 | 718篇 |
免费 | 48篇 |
国内免费 | 12篇 |
出版年
2023年 | 14篇 |
2022年 | 17篇 |
2021年 | 24篇 |
2020年 | 27篇 |
2019年 | 21篇 |
2018年 | 21篇 |
2017年 | 19篇 |
2016年 | 14篇 |
2015年 | 26篇 |
2014年 | 44篇 |
2013年 | 38篇 |
2012年 | 22篇 |
2011年 | 31篇 |
2010年 | 18篇 |
2009年 | 30篇 |
2008年 | 31篇 |
2007年 | 41篇 |
2006年 | 44篇 |
2005年 | 13篇 |
2004年 | 14篇 |
2003年 | 16篇 |
2002年 | 13篇 |
2001年 | 10篇 |
2000年 | 14篇 |
1999年 | 6篇 |
1998年 | 10篇 |
1997年 | 17篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 15篇 |
1992年 | 12篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 17篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有778条查询结果,搜索用时 265 毫秒
751.
Jing Zhang Baian Chen Jing Lu Yi Wu Shubo Wang Zitong Yao Liming Zhu Yanhua Qiao Quan Sun Wei Qin Qiao Zhao Jianping Jia Cuibai Wei 《Aging cell》2019,18(4)
Cerebral amyloid beta (Aβ) deposits are the main early pathology of Alzheimer's disease (AD). However, abundant Aβ deposits also occur spontaneously in the brains of many healthy people who are free of AD with advancing aging. A crucial unanswered question in AD prevention is why AD does not develop in some elderly people, despite the presence of Aβ deposits. The answer may lie in the composition of Aβ oligomer isoforms in the Aβ deposits of healthy brains, which are different from AD brains. However, which Aβ oligomer triggers the transformation from aging to AD pathogenesis is still under debate. Some researchers insist that the Aβ 12‐mer causes AD pathology, while others suggest that the Aβ dimer is the crucial molecule in AD pathology. Aged rhesus monkeys spontaneously develop Aβ deposits in the brain with striking similarities to those of aged humans. Thus, rhesus monkeys are an ideal natural model to study the composition of Aβ oligomer isoforms and their downstream effects on AD pathology. In this study, we found that Aβ deposits in aged monkey brains included 3‐mer, 5‐mer, 9‐mer, 10‐mer, and 12‐mer oligomers, but not 2‐mer oligomers. The Aβ deposits, which were devoid of Aβ dimers, induced glial pathology (microgliosis, abnormal microglia morphology, and astrocytosis), but not the subsequent downstream pathologies of AD, including Tau pathology, neurodegeneration, and synapse loss. Our results indicate that the Aβ dimer plays an important role in AD pathogenesis. Thus, targeting the Aβ dimer is a promising strategy for preventing AD. 相似文献
752.
Jian‐fei Yan Wen‐pin Qin Bo‐cheng Xiao Qian‐qian Wan Franklin R. Tay Li‐na Niu Kai Jiao 《Biological reviews of the Cambridge Philosophical Society》2020,95(4):960-985
In the progression of osteoarthritis, pathological calcification in the affected joint is an important feature. The role of these crystallites in the pathogenesis and progression of osteoarthritis is controversial; it remains unclear whether they act as a disease initiator or are present as a result of joint damage. Recent studies reported that the molecular mechanisms regulating physiological calcification of skeletal tissues are similar to those regulating pathological or ectopic calcification of soft tissues. Pathological calcification takes place when the equilibrium is disrupted. Calcium phosphate crystallites are identified in most affected joints and the presence of these crystallites is closely correlated with the extent of joint destruction. These observations suggest that pathological calcification is most likely to be a disease initiator instead of an outcome of osteoarthritis progression. Inhibiting pathological crystallite deposition within joint tissues therefore represents a potential therapeutic target in the management of osteoarthritis. 相似文献
753.
G. Lizard Y. Chardonnet M. C. Chignol J. Thivolet 《Virchows Archiv. B, Cell pathology including molecular pathology》1991,60(1):301-306
Flow cytometry and ultrastructural morphometry were used to study some characteristics of cells obtained by fusion with polyethylene-glycol
4000 between mouse fibroblasts 3T3.4E and normal human keratinocytes (3T3.4E × NHK) or hand wart human keratinocytes (3T3.4E
× HWK), at late passages. The cell cycle and the expression of human β2-microglobulin, human EGF-receptors (EGF-r), vimentin
were simultaneously studied by flow cytometry. Epithelial CaSki cells, derived from a human uterine carcinoma, expressing
high levels of β2-microglobulin, EGF-r and vimentin, were used as a positive control. In mouse fibroblasts 3T3.4E only vimentin
was expressed whereas in cells derived from fusion, human β2-microglobulin, human EGF-r and vimentin were detected. The cell
cycle analysis revealed that the peak position of G0/G1 differed with the cells (channel 11 for 3T3.4E cells, 13 for 3T3.4E
× HWK and 15 for 3T3.4E × NHK). The area of the cell compartments from each cell type was also different by quantitative ultrastructural
morphometry. The hybrid phenotype was maintained in late passages in cells (3T3.4E × NHK) and (3T3.4E × HWK), as shown by
the expression of human antigens, differences in DNA contents and nuclear area. Flow cytometry may be a very accurate and
precise tool for studying low antigenic expression. The combination of different methods including analysis of DNA content,
antigenic expression and ultrastructural morphometry confirmed that 3T3.4E, 3T3.4E × NHK and 3T3.4E × HWK cells are different
cell types. These techniques are complementary to cell phenotype analysis. We have thus given evidence that cell fusion between
mouse and human cells can lead to new cell types that retain human markers even after late passages, and that the combination
of three techniques (flow cytometry, ultrastructural morphometry and immunocytochemistry) is a very useful approach. 相似文献
754.
《American journal of human genetics》2022,109(3):457-470
- Download : Download high-res image (209KB)
- Download : Download full-size image
755.
756.
757.
Veronika Shavlokhova Christa Flechtenmacher Sameena Sandhu Maximilian Pilz Michael Vollmer Jürgen Hoffmann Michel Engel Christian Freudlsperger 《Journal of biophotonics》2020,13(9)
Real‐time microscopic imaging of freshly excised tissue enables a rapid bedside‐pathology. A possible application of interest is the detection of oral squamous cell carcinomas (OSCCs). The aim of this study was to analyze the sensitivity and specificity of ex vivo fluorescence confocal microscopy (FCM) for OSCCs and to compare confocal images visually and qualitatively with gold standard histopathology. Two hundred eighty ex vivo FCM images were prospectively collected and evaluated immediately after excision. Every confocal image was blindly assessed for the presence or absence of malignancy by two clinicians and one pathologist. The results were compared with conventional histopathology with hematoxylin and eosin staining. OSCCs were detected with a very high sensitivity of 0.991, specificity of 0.9527, positive predictive value of 0.9322 and negative predictive value of 0.9938. The results demonstrate the potential of ex vivo FCM in fresh tissue for rapid real‐time surgical pathology. 相似文献
758.
B. Arensburg 《Human Evolution》1996,11(2):139-145
Dental calculus has been often considered as a consequence of dietary habits, mainly related to the post Neolitic agricultural
development. The presence of fossilized bacteria in the Kebara 2 teeth, aged 60.000 years BP, and the similarity of oral pathologies
in pre and post Neolithic samples confirm the multifactorial etiology of oral diseases in general and dental calculus in particular. 相似文献
759.
Neprilysin Deficiency-Dependent Impairment of Cognitive Functions in a Mouse Model of Amyloidosis 总被引:1,自引:0,他引:1
Alzheimer’s disease, responsible for the vast majority of dementia cases in the elderly population, is caused by accumulation
of toxic levels of amyloid β peptide (Aβ) in the brain. Neprilysin is a major enzyme responsible for the degradation of Aβ in vivo. We have previously
shown that elevation of neprilysin levels in the brain delays the deposition of Aβ -plaques in a mouse model of amyloidosis
and that lack of neprilysin leads to increased Aβ generation and to signs of incipient neurodegeneration in mouse brains.
This study was designed to test whether low brain levels of neprilysin affect the amyloid pathology or perturb the learning
and memory performance of mice. Double-mutated mice carrying a targeted depletion of one allele of Mme, the gene encoding neprilysin, and over-expressing human amyloid precursor protein (APP), exhibited a reinforced amyloid
pathology in comparison with their APP transgenic littermates. Moreover, in contrast to their parental lines, these mice were
impaired in the Morris water maze learning and memory paradigm and showed facilitated extinction in the conditioned taste
aversion test. These data suggest that even a partial neprilysin deficiency, as is found during aging, exacerbates amyloid
pathology and may impair cognitive functions.
Special issue to Honor Dr. Akitane Mori. 相似文献
760.