首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   4965篇
  免费   302篇
  国内免费   2篇
  5269篇
  2024年   8篇
  2023年   16篇
  2022年   71篇
  2021年   81篇
  2020年   52篇
  2019年   71篇
  2018年   100篇
  2017年   87篇
  2016年   158篇
  2015年   263篇
  2014年   316篇
  2013年   337篇
  2012年   488篇
  2011年   428篇
  2010年   270篇
  2009年   243篇
  2008年   342篇
  2007年   268篇
  2006年   263篇
  2005年   222篇
  2004年   194篇
  2003年   170篇
  2002年   150篇
  2001年   129篇
  2000年   125篇
  1999年   112篇
  1998年   38篇
  1997年   28篇
  1996年   20篇
  1995年   21篇
  1994年   20篇
  1993年   17篇
  1992年   26篇
  1991年   23篇
  1990年   14篇
  1989年   11篇
  1988年   8篇
  1987年   4篇
  1986年   9篇
  1984年   4篇
  1982年   4篇
  1981年   3篇
  1977年   4篇
  1976年   4篇
  1974年   7篇
  1973年   3篇
  1972年   3篇
  1969年   4篇
  1967年   5篇
  1966年   5篇
排序方式: 共有5269条查询结果,搜索用时 15 毫秒
101.
Park SH  Oh HB  Seong WK  Kim CW  Cho SY  Yoo CK 《Proteomics》2007,7(20):3743-3758
Bacillus anthracis is a gram-positive bacterial organism responsible for anthrax. This organism has two pathogenic plasmids: pX01 and pX02. The genetic function of pX01, which comprises about 198 kb, is not known, except for a region called the pathogenic island, which contains three genes-pag, lef, and cya-that code for three toxic proteins. A 2-D difference gel electrophoresis (2-D DIGE) system was used to verify the existence of proteins controlled by the pX01 plasmid, and protein regulation data were obtained using DeCyder software. A total of 1728 proteins were identified in the wild-type strain of this organism and 1684 in the pX01 plasmid. Twenty-seven of these proteins disappeared and eight appeared when the pX01 plasmid was removed. An additional 52 proteins were downregulated and 15 were upregulated when this plasmid was removed. A total of 102 proteins have been identified using the MALDI-TOF method of analysis, including 49 whose functions are unknown. Among these, 31 participate in metabolic processes, two in cellular processes, 15 in the processing of genetic information, and five in the processing of extracellular information. Another seven proteins participate in bacterial virulence and pathogenesis. We investigated the functions of these proteins in other bacteria, particularly the B. anthracis derivative H9041. Bacterial growth differed between pX01+/pX02+ B. anthracis and its pX01-/pX02+ derivative as did the cytotoxicity of macrophages infected by pX01+/pX02+ B. anthracis and the pX01-pX02+ derivative. We also found that S100B protein levels increased in the host infected with pX01+/pX02+ B. anthracis or its pX01-/pX02+ derivative. These data suggest that the pX01 plasmid plays a key role in the regulation of protein functions in B. anthracis.  相似文献   
102.
Tomographic phase microscopy   总被引:1,自引:0,他引:1  
We report a technique for quantitative three-dimensional (3D) mapping of refractive index in live cells and tissues using a phase-shifting laser interferometric microscope with variable illumination angle. We demonstrate tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure. Our results will permit quantitative characterization of specimen-induced aberrations in high-resolution microscopy and have multiple applications in tissue light scattering.  相似文献   
103.
Molecular and Cellular Biochemistry - Electron transfer occurs through heme-Fe across the cytochrome c protein. The current models of long range electron transfer pathways in proteins include...  相似文献   
104.
Molecular Biology Reports - Mu-2-related death-inducing (MuD) gene is involved in apoptosis in tumor cells. Although we have previously produced mouse monoclonal antibodies (MAbs) that specifically...  相似文献   
105.
In aquaculture, feeding is essential for the maintenance of metabolic processes and homoeostasis of fish. However, fasting acts as a stressor. In this study, we investigated the effect of circadian rhythm under various LED wavelengths [blue (460 nm), green (520 nm) and red (630 nm)] and two light intensities (0.3 and 0.6 W m?2) over a 9-days period in the olive flounder (Paralichthys olivaceus). We analysed clock genes like period 2 (Per 2) and cryptochrome 1 (Cry 1), and serotonin and arylalkylamine-N-acetyltransferase 2 (AANAT 2), which control circadian rhythms. Per 2, Cry 1, serotonin and AANAT 2 were significantly decreased during the starvation period compared to the normal feeding group. Nevertheless, their levels increased in the groups exposed to green- and blue LED light during the experimental period. These results confirmed that green and blue wavelengths are effective in maintaining the circadian rhythm in olive flounder.  相似文献   
106.
Nature experiences have been linked to mental and physical health. Despite the importance of understanding what determines individual variation in nature experience, the role of genes has been overlooked. Here, using a twin design (TwinsUK, number of individuals = 2,306), we investigate the genetic and environmental contributions to a person’s nature orientation, opportunity (living in less urbanized areas), and different dimensions of nature experience (frequency and duration of public nature space visits and frequency and duration of garden visits). We estimate moderate heritability of nature orientation (46%) and nature experiences (48% for frequency of public nature space visits, 34% for frequency of garden visits, and 38% for duration of garden visits) and show their genetic components partially overlap. We also find that the environmental influences on nature experiences are moderated by the level of urbanization of the home district. Our study demonstrates genetic contributions to individuals’ nature experiences, opening a new dimension for the study of human–nature interactions.

Nature experiences have been linked to mental and physical health. This twin study reveals genetic influences on an individual’s orientation towards nature and nature experiences, opening a new dimension to understanding human-nature interactions.  相似文献   
107.
Corn silk (Stigma Maydis) has been utilized as an important herb against obesity by Chinese, Korean, and Native Americans, but its phytochemicals and mechanisms(s) against obesity have not been deciphered completely. This study aimed to identify promising bioactive constituents and mechanism of action(s) of corn silk (CS) against obesity via network pharmacology. The compounds from CS were identified using Gas Chromatography Mass Spectrometry (GC-MS) and were confirmed ultimately by Lipinski’s rule via SwissADME. The relationships of the compound-targets or obesity-related targets were confirmed by public bioinformatics. The signaling pathways related to obesity, protein-protein interaction (PPI), and signaling pathways-targets-bioactives (STB) were constructed, visualized, and analyzed by RPackage. Lastly, Molecular Docking Test (MDT) was performed to validate affinity between ligand(s) and protein(s) on key signaling pathway(s). We identified a total of 36 compounds from CS via GC-MS, all accepted by Lipinski’s rule. The number of 36 compounds linked to 154 targets, 85 among 154 targets related directly to obesity-targets (3028 targets). Of the final 85 targets, we showed that the PPI network (79 edges, 357 edges), 12 signaling pathways on a bubble chart, and STB network (67 edges, 239 edges) are considered as therapeutic components. The MDT confirmed that two key activators (β-Amyrone, β-Stigmasterol) bound most stably to PPARA, PPARD, PPARG, FABP3, FABP4, and NR1H3 on the PPAR signaling pathway, also, three key inhibitors (Neotocopherol, Xanthosine, and β-Amyrone) bound most tightly to AKT1, IL6, FGF2, and PHLPP1 on the PI3K-Akt signaling pathway. Overall, we provided promising key signaling pathways, targets, and bioactives of CS against obesity, suggesting crucial pharmacological evidence for further clinical testing.  相似文献   
108.
Use of electrophoretic enzyme patterns for streptomycete systematics   总被引:1,自引:0,他引:1  
Abstract The relative electrophoretic mobilities of various enzymes from 24 different streptomycetes were determined on polyacrylamide gels in order to examine the relatedness of species and strains of the genus Streptomyces . Of 11 different enzymes tested in this study, hexokinase, glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase showed a limited number of constant and reproducible polymorphic enzyme patterns, by comparing which the inter-specific relationships could be examined. In contrast, glucose dehydrogenase, alcohol dehydrogenase, 3-hydroxybutyrate dehydrogenase, phosphoglucose isomerase, peroxidase and esterase exhibited either weak non-reproducible or highly heterogeneous band patterns which were suitable for dissecting the strains within a species and a cluster group.  相似文献   
109.
Genetic differentiation between populations is determined by various factors, including gene flow, selection, mutation, and genetic drift. Among these, gene flow is known to counter genetic differentiation. The genus Eranthis, an early flowering perennial herb, can serve as a good model to study genetic differentiation and gene flow due to its easily detectable population characteristics and known reproductive strategies, which can be associated with gene flow patterns. Eranthis populations are typically small and geographically separated from the others. Moreover, previous studies and our own observations suggest that seed and pollen dispersal between Eranthis populations is highly unlikely and therefore, currently, gene flow may not be probable in this genus. Based on these premises, we hypothesized that the genetic differentiation between the Eranthis populations would be significant, and that the genetic differentiation would not sensitively reflect geographic distance in the absence of gene flow. To test these hypotheses, genetic differentiation, genetic distance, isolation by distance, historical gene flow, and bottlenecks were analyzed in four species of this genus. Genetic differentiation was significantly high, and in many cases, extremely high. Moreover, genetic differentiation and geographic distance were positively correlated in most cases. We provide possible explanations for these observations. First, we suggest that the combination of the marker type used in our study (chloroplast microsatellites), genetic drift, and possibly selection might have resulted in the extremely high genetic differentiation observed herein. Additionally, we provide the possibility that genetic distance reflects geographic distance through historical gene flow, or adaptation in the absence of historical gene flow. Nevertheless, our explanations can be more rigorously examined and further refined through additional observations and various population genetic analyses. In particular, we suggest that other accessible populations of the genus Eranthis should be included in future studies to better characterize the intriguing population dynamics of this genus.  相似文献   
110.
BackgroundPreclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.Methods and findingsIn a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules.ConclusionsNight-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Wi-Sun Ryu and colleagues investigate the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in ischemic stroke.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号