全文获取类型
收费全文 | 1382篇 |
免费 | 153篇 |
出版年
2021年 | 21篇 |
2020年 | 18篇 |
2019年 | 18篇 |
2018年 | 26篇 |
2017年 | 17篇 |
2016年 | 26篇 |
2015年 | 40篇 |
2014年 | 50篇 |
2013年 | 56篇 |
2012年 | 83篇 |
2011年 | 67篇 |
2010年 | 59篇 |
2009年 | 40篇 |
2008年 | 56篇 |
2007年 | 51篇 |
2006年 | 47篇 |
2005年 | 52篇 |
2004年 | 51篇 |
2003年 | 36篇 |
2002年 | 37篇 |
2001年 | 38篇 |
2000年 | 39篇 |
1999年 | 28篇 |
1998年 | 15篇 |
1997年 | 12篇 |
1996年 | 13篇 |
1995年 | 14篇 |
1993年 | 15篇 |
1992年 | 25篇 |
1991年 | 26篇 |
1990年 | 21篇 |
1989年 | 19篇 |
1988年 | 26篇 |
1987年 | 23篇 |
1986年 | 22篇 |
1985年 | 24篇 |
1984年 | 21篇 |
1983年 | 16篇 |
1981年 | 14篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 12篇 |
1977年 | 18篇 |
1975年 | 14篇 |
1974年 | 17篇 |
1973年 | 18篇 |
1972年 | 16篇 |
1970年 | 12篇 |
1969年 | 20篇 |
1968年 | 13篇 |
排序方式: 共有1535条查询结果,搜索用时 15 毫秒
61.
Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity 总被引:2,自引:0,他引:2
Ding M Feng R Wang SY Bowman L Lu Y Qian Y Castranova V Jiang BH Shi X 《The Journal of biological chemistry》2006,281(25):17359-17368
Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo. 相似文献
62.
Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the Src oncoprotein. 总被引:9,自引:0,他引:9
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
63.
A significant macrophage and T-cell infiltrate commonly occurs in inflammatory joint conditions such as rheumatoid arthritis
that have significant bone destruction. Cytokines produced by activated macrophages and T cells are implicated in arthritis
pathogenesis and are involved in osteoclast-mediated bone resorption. The scope of the present review is to analyze current
knowledge and to provide a better understanding of how macrophage-derived factors promote the differentiation of a novel T-helper
subset (Th17) that promotes osteoclast formation and activation. 相似文献
64.
Karim S Essenberg RC Dillwith JW Tucker JS Bowman AS Sauer JR 《Insect biochemistry and molecular biology》2002,32(12):159-1721
Prostaglandin E(2) (PGE(2)) stimulates secretion of tick salivary gland proteins via a phosphoinositide signaling pathway and mobilization of intracellular Ca(2+) (). Highly conserved intracellular SNARE (soluble NSF attachment protein receptors) complex proteins are associated with the mechanism of protein secretion in vertebrate and invertebrate neuronal and non-neuronal cells. Proteins in the salivary glands of partially fed female lone star ticks cross-react individually with antibodies to synaptobrevin-2 (vesicle (v)-SNARE), syntaxin-1A, syntaxin-2 and SNAP-25 (target (t)-SNAREs), cytosolic alpha/beta SNAP and NSF (N-ethylmaleimide-sensitive fusion protein), Ca(2+) sensitive synaptotagmin, vesicle associated synaptophysin, and regulatory cell trafficking GTPases Rab3A and nSec1. V-SNARE and t-SNARE proteins form an SDS-resistant, boiling sensitive core complex in the salivary glands. Antibodies to SNARE complex proteins inhibit PGE(2)-stimulated secretion of anticoagulant protein in permeabilized tick salivary glands. We conclude that SNARE and cell trafficking regulatory proteins are present and functioning in the process of PGE(2)-stimulated Ca(2+) regulated protein secretion in tick salivary glands. 相似文献
65.
Exopolysaccharides (EPSs) are high molecular weight carbohydrate polymers that make up a substantial component of the extracellular polymers surrounding most microbial cells in the marine environment. EPSs constitute a large fraction of the reduced carbon reservoir in the ocean and enhance the survival of marine bacteria by influencing the physicochemical environment around the bacterial cell. Microbial EPSs are abundant in the Antarctic marine environment, for example, in sea ice and ocean particles, where they may assist microbial communities to endure extremes of temperature, salinity, and nutrient availability. The microbial biodiversity of Antarctic ecosystems is relatively unexplored. Deep-sea hydrothermal vent environments are characterized by high pressure, extreme temperature, and heavy metals. The commercial value of microbial EPSs from these habitats has been established recently. Extreme environments offer novel microbial biodiversity that produces varied and promising EPSs. The biotechnological potential of these biopolymers from hydrothermal vent environments as well as from Antarctic marine ecosystems remains largely untapped. 相似文献
66.
Fernandez-Piquer J Bowman JP Ross T Tamplin ML 《Applied and environmental microbiology》2011,77(24):8687-8695
Vibrio parahaemolyticus is an indigenous bacterium of marine environments. It accumulates in oysters and may reach levels that cause human illness when postharvest temperatures are not properly controlled and oysters are consumed raw or undercooked. Predictive models were produced by injecting Pacific oysters (Crassostrea gigas) with a cocktail of V. parahaemolyticus strains, measuring viability rates at storage temperatures from 3.6 to 30.4°C, and fitting the data to a model to obtain parameter estimates. The models were evaluated with Pacific and Sydney Rock oysters (Saccostrea glomerata) containing natural populations of V. parahaemolyticus. V. parahaemolyticus viability was measured by direct plating samples on thiosulfate-citrate-bile salts-sucrose (TCBS) agar for injected oysters and by most probable number (MPN)-PCR for oysters containing natural populations. In parallel, total viable bacterial counts (TVC) were measured by direct plating on marine agar. Growth/inactivation rates for V. parahaemolyticus were −0.006, −0.004, −0.005, −0.003, 0.030, 0.075, 0.095, and 0.282 log10 CFU/h at 3.6, 6.2, 9.6, 12.6, 18.4, 20.0, 25.7, and 30.4°C, respectively. The growth rates for TVC were 0.015, 0.023, 0.016, 0.048, 0.055, 0.071, 0.133, and 0.135 log10 CFU/h at 3.6, 6.2, 9.3, 14.9, 18.4, 20.0, 25.7, and 30.4°C, respectively. Square root and Arrhenius-type secondary models were generated for V. parahaemolyticus growth and inactivation kinetic data, respectively. A square root model was produced for TVC growth. Evaluation studies showed that predictive growth for V. parahaemolyticus and TVC were “fail safe.” The models can assist oyster companies and regulators in implementing management strategies to minimize V. parahaemolyticus risk and enhancing product quality in supply chains. 相似文献
67.
Tao Ke Filipe Marques Gonçalves Cinara Ludvig Gonçalves Alessandra Antunes dos Santos João B.T. Rocha Marcelo Farina Anatoly Skalny Aristidis Tsatsakis Aaron B. Bowman Michael Aschner 《生物化学与生物物理学报:疾病的分子基础》2019,1865(8):2068-2081
Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity. 相似文献
68.
Nick Bowman Dong Liu Patrick Paczkowski Jon Chen John Rossi Sean Mackay Adrian Bot Jing Zhou 《Proteomics》2020,20(13)
Highly multiplexed single‐cell functional proteomics has emerged as one of the next‐generation toolkits for a deeper understanding of functional heterogeneity in cell. Different from the conventional population‐based bulk and single‐cell RNA‐Seq assays, the microchip‐based proteomics at the single‐cell resolution enables a unique identification of highly polyfunctional cell subsets that co‐secrete many proteins from live single cells and most importantly correlate with patient response to a therapy. The 32‐plex IsoCode chip technology has defined a polyfunctional strength index (PSI) of pre‐infusion anti‐CD19 chimeric antigen receptor (CAR)‐T products, that is significantly associated with patient response to the CAR‐T cell therapy. To complement the clinical relevance of the PSI, a comprehensive visualization toolkit of 3D uniform manifold approximation and projection (UMAP) and t‐distributed stochastic neighbor embedding (t‐SNE) in a proteomic analysis pipeline is developed, providing more advanced analytical algorithms for more intuitive data visualizations. The UMAP and t‐SNE of anti‐CD19 CAR‐T products reveal distinct cytokine profiles between nonresponders and responders and demonstrate a marked upregulation of antitumor‐associated cytokine signatures in CAR‐T cells from responding patients. Using this powerful while user‐friendly analytical tool, the multi‐dimensional single‐cell data can be dissected from complex immune responses and uncover underlying mechanisms, which can promote correlative biomarker discovery, improved bioprocessing, and personalized treatment development. 相似文献
69.
Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups 总被引:36,自引:0,他引:36
Peter B. Reich Michael B. Walters David S. Ellsworth James M. Vose John C. Volin Charles Gresham William D. Bowman 《Oecologia》1998,114(4):471-482
Based on prior evidence of coordinated multiple leaf trait scaling, we hypothesized that variation among species in leaf
dark respiration rate (R
d) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic
capacity (A
max). However, it is not known whether such scaling, if it exists, is similar among disparate biomes and plant functional types.
We tested this idea by examining the interspecific relationships between R
d measured at a standard temperature and leaf life-span, N, SLA and A
max for 69 species from four functional groups (forbs, broad-leafed trees and shrubs, and needle-leafed conifers) in six biomes
traversing the Americas: alpine tundra/subalpine forest, Colorado; cold temperate forest/grassland, Wisconsin; cool temperate
forest, North Carolina; desert/shrubland, New Mexico; subtropical forest, South Carolina; and tropical rain forest, Amazonas,
Venezuela. Area-based R
d was positively related to area-based leaf N within functional groups and for all species pooled, but not when comparing among
species within any site. At all sites, mass-based R
d (R
d-mass) decreased sharply with increasing leaf life-span and was positively related to SLA and mass-based A
max and leaf N (leaf N
mass). These intra-biome relationships were similar in shape and slope among sites, where in each case we compared species belonging
to different plant functional groups. Significant R
d-mass−N
mass relationships were observed in all functional groups (pooled across sites), but the relationships differed, with higher R
d at any given leaf N in functional groups (such as forbs) with higher SLA and shorter leaf life-span. Regardless of biome
or functional group, R
d-mass was well predicted by all combinations of leaf life-span, N
mass and/or SLA (r
2≥ 0.79, P < 0.0001). At any given SLA, R
d-mass rises with increasing N
mass and/or decreasing leaf life-span; and at any level of N
mass, R
d-mass rises with increasing SLA and/or decreasing leaf life-span. The relationships between R
d and leaf traits observed in this study support the idea of a global set of predictable interrelationships between key leaf
morphological, chemical and metabolic traits.
Received: 23 May 1997 / Accepted: 16 December 1997 相似文献
70.
J P Dubey A P Gendron-Fitzpatrick A L Lenhard D Bowman 《The Journal of protozoology》1988,35(4):528-530
Toxoplasma gondii was found in tissues of a six-year-old female Pallas cat (Felis manul) from the Milwaukee County Zoo. Toxoplasma gondii meronts (types D and E), gamonts, and oocysts were present in the epithelium of the small intestine. Numerous unsporulated oocysts were present in the intestinal lumen. The cat died of acute, overwhelming toxoplasmosis. Necrotic enteritis, multifocal necrotizing granulomatous hepatitis, and pneumonia were the prominent lesions. 相似文献