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991.
992.
Effect of Dextran 500 on Radial Migration of Erythrocytes in Postcapillary Venules at Low Flow Rates
Recently, we reported that collision efficiency (fraction of total collisions that result in the formation of aggregates) between red blood cells was an important factor in the formation of aggregates in postcapillary venules. In the present study, we focus on how high molecular weight dextran influences the overall radial migration trend of red blood cells in the postcapillary venule along a longitudinal distance of 50 μm from the bifurcation which would in turn affect collision behavior of these cells. A radial migration index, which defines the extent of radial migration of individual cells relative to the vessel center, was found to have a larger magnitude after infusion of dextran (1.9 ± 2.73) compared to that before dextran infusion (1.48 ± 3.89). This implied that dextran-induced aggregation might provide an external force to actively move cells towards the centerline of the vessel, which could contribute to the greater number of red blood cells participating in collision (16% increase) and aggregate formation. Further analysis of the collision behavior of individual red blood cells revealed that collision frequencies of individual cells decreased from a wide range (1 to 14) to a narrow range (1 to 5) after dextran treatment, indicating the alteration of collision behavior of red blood cells by the presence of aggregates along the flow stream. 相似文献
993.
Aiming to develop anticancer agents, synthesis and in vitro evaluation of aromatic dienyl diketone derivatives were carried out. All the aromatic (Z.E)-dienyl diketones synthesized exhibit strong in vitro inhibition of tumor cell growth against Colon cell line. 相似文献
994.
BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity
Eui-Jun Kim Peng Liu Shengjie Zhang Kristine Donahue Yidan Wang Jennifer
L Schehr Serena
K Wolfe Amber Dickerson Li Lu Lixin Rui Xuehua Zhong Kari
B Wisinski Min Yu Aussie Suzuki Joshua
M Lang Irene
M Ong Wei Xu 《Nucleic acids research》2021,49(21):12211
Subunits of the chromatin remodeler SWI/SNF are the most frequently disrupted genes in cancer. However, how post-translational modifications (PTM) of SWI/SNF subunits elicit epigenetic dysfunction remains unknown. Arginine-methylation of BAF155 by coactivator-associated arginine methyltransferase 1 (CARM1) promotes triple-negative breast cancer (TNBC) metastasis. Herein, we discovered the dual roles of methylated-BAF155 (me-BAF155) in promoting tumor metastasis: activation of super-enhancer-addicted oncogenes by recruiting BRD4, and repression of interferon α/γ pathway genes to suppress host immune response. Pharmacological inhibition of CARM1 and BAF155 methylation not only abrogated the expression of an array of oncogenes, but also boosted host immune responses by enhancing the activity and tumor infiltration of cytotoxic T cells. Moreover, strong me-BAF155 staining was detected in circulating tumor cells from metastatic cancer patients. Despite low cytotoxicity, CARM1 inhibitors strongly inhibited TNBC cell migration in vitro, and growth and metastasis in vivo. These findings illustrate a unique mechanism of arginine methylation of a SWI/SNF subunit that drives epigenetic dysregulation, and establishes me-BAF155 as a therapeutic target to enhance immunotherapy efficacy. 相似文献
995.
Houssier M Raoul W Lavalette S Keller N Guillonneau X Baragatti B Jonet L Jeanny JC Behar-Cohen F Coceani F Scherman D Lachapelle P Ong H Chemtob S Sennlaub F 《PLoS medicine》2008,5(2):e39
Background
In the Western world, a major cause of blindness is age-related macular degeneration (AMD). Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the “wet” form of AMD. In contrast, very little is known about the mechanisms of the predominant, “dry” form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD.Methods and Findings
We here show that deficiency of CD36, which participates in outer segment (OS) phagocytosis by the retinal pigment epithelium (RPE) in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR) and CD36−/− mice). Furthermore, these animals developed significant age related choroidal involution reflected in a 100%–300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF) expression upon OS or antibody stimulation in vitro. CD36−/− mice express reduced levels of COX2 and VEGF in vivo, and COX2−/− mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency.Conclusions
CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies. 相似文献996.
997.
Objective: In order to characterize the regulation of resistin gene expression, we explore the effect of tumornecrosis factor‐α (TNF‐α) on resistin mRNA expression and its underlying mechanism in 3T3‐L1 adipocytes. Methods and Procedures: Differentiated 3T3‐L1 adipocytes were treated for 24 h with 0–10 ng/ml of TNF‐α or with 2.5 ng/ml of TNF‐α for 0–24 h, and then resistin mRNA levels were measured by northern blotting. To further explore the involvement of nitric oxide (NO) in TNF‐α–regulated resistin expression, the effect of the NO donor, sodium nitroprusside (SNP), on resistin mRNA levels in adipocytes and the effect of the nitric oxide synthase (NOS) inhibitors, NG‐nitro‐l ‐arginine methyl ester (l ‐NAME), and S, S′?1,3‐phenylene‐bis(1,2‐ethanediyl)‐bis‐isothiourea·2HBr (PBITU), on the TNF‐α effect in adipocytes were examined. The effects of TNF‐α on inducible NOS (iNOS) protein expression in adipocytes were also measured by western blotting. Results: Our results showed that TNF‐α caused a dose‐dependent reduction in resistin mRNA levels. This effect seemed to be associated with the TNF‐α–induced expression of iNOS. The results showed that TNF‐α induced iNOS expression and release of NO after 24‐h treatment of differentiated 3T3‐L1 adipocytes. Pretreatment with l ‐NAME and PBITU significantly reversed the TNF‐α–induced downregulation of resistin expression, while treatment with SNP mimicked the inhibitory effect of TNF‐α on resistin expression. In addition, pretreatment with protein tyrosine kinase (PTK) inhibitors, genistein and AG‐1288, prevented TNF‐α–induced iNOS expression and subsequent resistin downregulation. Discussion: Our data suggest that TNF‐α suppresses resistin expression by inducing iNOS expression, thus causing overproduction of NO, which downregulates resistin gene expression. 相似文献
998.
Effect of Radiation Quality on Growth and Photosynthesis of Acacia mangium Seedlings 总被引:1,自引:0,他引:1
Radiation quality was an important environmental cue to stimulate seed germination in Acacia mangium. The photo-synthetic CO2 assimilation rate, dark respiration rate, total biomass, and relative growth rate of seedlings grown under monochromatic radiation were significantly lower than those of seedlings grown under full spectrum radiation. Blue and red radiation induced shade-avoidance and shade-tolerant responses of A. mangium seedlings, respectively. 相似文献
999.
Background
The Rasd1 protein is a dexamethasone induced monomeric Ras-like G protein that oscillates in the suprachiasmatic nucleus (SCN). Previous studies have shown that Rasd1 modulates multiple signaling cascades. However, it is still unclear exactly how Rasd1 carries out its function. Studying protein-protein interactions involving Rasd1 may provide insights into its biological functions in different contexts. 相似文献1000.
Protection of salvia miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats dual mechanisms involved. 总被引:4,自引:0,他引:4
Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 microg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM. 相似文献