全文获取类型
收费全文 | 11071篇 |
免费 | 972篇 |
国内免费 | 5篇 |
专业分类
12048篇 |
出版年
2023年 | 48篇 |
2022年 | 106篇 |
2021年 | 179篇 |
2020年 | 116篇 |
2019年 | 148篇 |
2018年 | 194篇 |
2017年 | 172篇 |
2016年 | 321篇 |
2015年 | 479篇 |
2014年 | 569篇 |
2013年 | 671篇 |
2012年 | 881篇 |
2011年 | 869篇 |
2010年 | 538篇 |
2009年 | 502篇 |
2008年 | 688篇 |
2007年 | 694篇 |
2006年 | 638篇 |
2005年 | 652篇 |
2004年 | 645篇 |
2003年 | 589篇 |
2002年 | 567篇 |
2001年 | 105篇 |
2000年 | 70篇 |
1999年 | 115篇 |
1998年 | 181篇 |
1997年 | 111篇 |
1996年 | 97篇 |
1995年 | 96篇 |
1994年 | 100篇 |
1993年 | 91篇 |
1992年 | 68篇 |
1991年 | 60篇 |
1990年 | 44篇 |
1989年 | 47篇 |
1988年 | 44篇 |
1987年 | 44篇 |
1986年 | 37篇 |
1985年 | 49篇 |
1984年 | 36篇 |
1983年 | 50篇 |
1982年 | 65篇 |
1981年 | 41篇 |
1980年 | 25篇 |
1979年 | 33篇 |
1978年 | 35篇 |
1977年 | 19篇 |
1976年 | 20篇 |
1975年 | 16篇 |
1973年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
221.
Engelborghs S Maertens K Vloeberghs E Aerts T Somers N Mariën P De Deyn PP 《Neurochemistry international》2006,48(4):286-295
To improve clinical, neuropsychological and behavioural characterisation of the cerebrospinal fluid (CSF) biomarkers beta-amyloid((1-42)) protein (Abeta42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was set up. Patients with probable Alzheimer's disease (AD) (n=201), AD with cerebrovascular disease (CVD) (AD+CVD) (n=33), frontotemporal dementia (FTD) (n=27), dementia with Lewy bodies (DLB) (n=22) and healthy controls (n=148) were included. All patients underwent neuropsychological examination and behavioural assessment by means of a battery of behavioural assessment scales. CSF was obtained by lumbar puncture and levels of Abeta42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF Abeta42 levels and aggressiveness (Spearman: r=-0.223; p=0.002) and positive correlations with age at inclusion (r=0.195; p=0.006), age at onset (r=0.205; p=0.003) and MMSE scores (r=0.198; p=0.005) were found in AD. In AD+CVD, CSF Abeta42 levels were correlated with MMSE (r=0.482; p=0.006), Hierarchic Dementia Scale (r=0.503; p=0.017) and Boston Naming Test (r=0.516; p=0.012) scores. In controls, age was positively correlated with CSF tau (r=0.465; p<0.001) and P-tau181 levels (r=0.312; p<0.001). CSF tau and P-tau181 levels correlated significantly in all groups, whereas CSF Abeta42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF Abeta42 levels and aggressiveness were found in AD patients. CSF Abeta42 seems to be a stage marker for AD (+/-CVD) given the positive correlations with neuropsychological test results suggesting that CSF Abeta42 might be of help for monitoring disease progression. Different correlations between age and CSF biomarker levels were obtained in healthy controls compared to AD patients, indicating that AD-induced pathophysiological processes change age-dependent regulation of CSF biomarker levels. 相似文献
222.
Karen F Chambers Joanna F Pearson Davide Pellacani Naveed Aziz Miodrag Gužvić Christoph A Klein Shona H Lang 《Journal of biomedical science》2011,18(1):45
Background
Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process. 相似文献223.
James C. Kathilankal Thomas J. Mozdzer José D. Fuentes Karen J. McGlathery Paolo D’Odorico Jay C. Zieman 《Hydrobiologia》2011,669(1):167-181
Physiological measurements were used to investigate the dependence of photosynthesis on light, temperature, and intercellular
carbon dioxide (CO2) levels in the C4 marsh grass Spartina alterniflora. Functional relationships between these environmental variables and S. alterniflora physiological responses were then used to improve C4-leaf photosynthesis models. Field studies were conducted in monocultures of S. alterniflora in Virginia, USA. On average, S. alterniflora exhibited lower light saturation values (~1000 μmol m−2 s−1) than observed in other C4 plants. Maximum carbon assimilation rates and stomatal conductance to water vapor diffusion were 36 μmol (CO2) m−2 s−1 and 200 mmol (H2O) m−2 s−1, respectively. Analysis of assimilation-intercellular CO2 and light response relationships were used to determine Arrhenius-type temperature functions for maximum rate of carboxylation
(V
cmax), phosphoenolpyruvate carboxylase activity (V
pmax), and maximum electron transport rate (J
max). Maximum V
cmax values of 105 μmol m−2 s−1 were observed at the leaf temperature of 311 K. Optimum V
pmax values (80.6 μmol m−2 s−1) were observed at the foliage temperature of 308 K. The observed V
pmax values were lower than those in other C4 plants, whereas V
cmax values were higher, and more representative of C3 plants. Optimum J
max values reached 138 μmol (electrons) m−2 s−1 at the foliage temperature of 305 K. In addition, the estimated CO2 compensation points were in the range of C3 or C3–C4 intermediate plants, not those typical of C4 plants. The present results indicate the possibility of a C3–C4 intermediate or C4-like photosynthetic mechanism rather than the expected C4-biochemical pathway in S. alterniflora under field conditions. In a scenario of atmospheric warming and increased atmospheric CO2 concentrations, S. alterniflora will likely respond positively to both changes. Such responses will result in increased S. alterniflora productivity, which is uncharacteristic of C4 plants. 相似文献
224.
225.
Understanding traits influencing the distribution of genetic diversity has major ecological and evolutionary implications for host–parasite interactions. The genetic structure of parasites is expected to conform to that of their hosts, because host dispersal is generally assumed to drive parasite dispersal. Here, we used a meta‐analysis to test this paradigm and determine whether traits related to host dispersal correctly predict the spatial co‐distribution of host and parasite genetic variation. We compiled data from empirical work on local adaptation and host–parasite population genetic structure from a wide range of taxonomic groups. We found that genetic differentiation was significantly lower in parasites than in hosts, suggesting that dispersal may often be higher for parasites. A significant correlation in the pairwise genetic differentiation of hosts and parasites was evident, but surprisingly weak. These results were largely explained by parasite reproductive mode, the proportion of free‐living stages in the parasite life cycle and the geographical extent of the study; variables related to host dispersal were poor predictors of genetic patterns. Our results do not dispel the paradigm that parasite population genetic structure depends on host dispersal. Rather, we highlight that alternative factors are also important in driving the co‐distribution of host and parasite genetic variation. 相似文献
226.
227.
Yasuo Ido Albert Duranton Fan Lan Karen A. Weikel Lionel Breton Neil B. Ruderman 《PloS one》2015,10(2)
The aging process is perceived as resulting from a combination of intrinsic factors such as changes in intracellular signaling and extrinsic factors, most notably environmental stressors. In skin, the relationship between intrinsic changes and keratinocyte function is not clearly understood. Previously, we found that increasing the activity of AMP-activated protein kinase (AMPK) suppressed senescence in hydrogen peroxide (H2O2)-treated human primary keratinocytes, a model of oxidative stress-induced cellular aging. Using this model in the present study, we observed that resveratrol, an agent that increases the activities of both AMPK and sirtuins, ameliorated two age-associated phenotypes: cellular senescence and proliferative dysfunction. In addition, we found that treatment of keratinocytes with Ex527, a specific inhibitor of sirtuin 1 (SIRT1), attenuated the ability of resveratrol to suppress senescence. In keeping with the latter observation, we noted that compared to non-senescent keratinocytes, senescent cells lacked SIRT1. In addition to these effects on H2O2-induced senescence, resveratrol also prevented the H2O2-induced decrease in proliferation (as indicated by 3H-thymidine incorporation) in the presence of insulin. This effect was abrogated by inhibition of AMPK but not SIRT1. Compared to endothelium, we found that human keratinocytes expressed relatively high levels of Forkhead box O3 (FOXO3), a downstream target of both AMPK and SIRT1. Treatment of keratinocytes with resveratrol transactivated FOXO3 and increased the expression of its target genes including catalase. Resveratrol’s effects on both senescence and proliferation disappeared when FOXO3 was knocked down. Finally, we performed an exploratory study which showed that skin from humans over 50 years old had lower AMPK activity than skin from individuals under age 20. Collectively, these findings suggest that the effects of resveratrol on keratinocyte senescence and proliferation are regulated by the AMPK-FOXO3 pathway and in some situations, but not all, by SIRT1. 相似文献
228.
Proteomics of Colwellia psychrerythraea at subzero temperatures – a life with limited movement,flexible membranes and vital DNA repair 下载免费PDF全文
Karen A. Cameron Emma Timmins‐Schiffman Karen Junge 《Environmental microbiology》2015,17(7):2319-2335
The mechanisms that allow psychrophilic bacteria to remain metabolically active at subzero temperatures result from form and function of their proteins. We present first proteomic evidence of physiological changes of the marine psychrophile Colwellia psychrerythraea 34H (Cp34H) after exposure to subzero temperatures (?1, and ?10°C in ice) through 8 weeks. Protein abundance was compared between different treatments to understand the effects of temperature and time, independently and jointly, within cells transitioning to, and being maintained in ice. Parallel [3H]‐leucine and [3H]–thymidine incubations indicated active protein and DNA synthesis to ?10°C. Mass spectrometry‐based proteomics identified 1763 proteins across four experimental treatments. Proteins involved in osmolyte regulation and polymer secretion were found constitutively present across all treatments, suggesting that they are required for metabolic success below 0°C. Differentially abundant protein groups indicated a reallocation of resources from DNA binding to DNA repair and from motility to chemo‐taxis and sensing. Changes to iron and nitrogen metabolism, cellular membrane structures, and protein synthesis and folding were also revealed. By elucidating vital strategies during life in ice, this study provides novel insight into the extensive molecular adaptations that occur in cold‐adapted marine organisms to sustain cellular function in their habitat. 相似文献
229.
RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity 总被引:2,自引:0,他引:2 下载免费PDF全文
Jenkins D Seelow D Jehee FS Perlyn CA Alonso LG Bueno DF Donnai D Josifova D Josifiova D Mathijssen IM Morton JE Orstavik KH Sweeney E Wall SA Marsh JL Nurnberg P Passos-Bueno MR Wilkie AO 《American journal of human genetics》2007,80(6):1162-1170
Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. In 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis--an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components--and provides a new molecular target for studies of obesity. 相似文献
230.