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《Acta histochemica》2022,124(8):151955
BackgroundAngiogenesis is an essential physiological process in the growth and metastasis of primary tumors. Ca2+ signaling is crucial for tumor angiogenesis. The purpose of this study was to detect the potential role of Ca2+ permeable transient receptor potential vanilloid-3 (TRPV3) in the angiogenesis of non-small cell lung cancer (NSCLC).MethodsSmall interfering RNA was used to down-regulate TRPV3 expression in A549 cells. A laser scanning confocal microscope was used to examine intracellular calcium concentration ([Ca2+]i). Human umbilical vein endothelial cells (HUVECs) tube formation and migration assay, Western blot, MTT and ELISA were performed to detect the potential mechanisms of TRPV3 in tumor angiogenesis. A mouse tumor xenograft model was performed to expound the effects of TRPV3 on tumor cell growth.ResultsInhibition of TRPV3 reduced [Ca2+]i and protein expressions of VEGF and HIF-1α in A549 cells. Moreover, HIF-1α depletion decreased the secretion and expression of VEGF. Depletion of TRPV3 inhibited HUVECs proliferation, tube formation and migration induced by conditioned medium. And TRPV3 inhibition could decrease the volume of xenograft tumors and MVD of CD34+ cells. The expression levels of HIF-1α, VEGF and p-CaMKП in the xenograft tumors in RuR and siTRPV3 groups was reduced.ConclusionsTRPV3 calcium channel protein may play a key role in NSCLC angiogenesis. TRPV3 could promote the angiogenesis through HIF-1α-VEGF signaling pathway. Targeting TRPV3 channel protein by novel approaches would be useful for reversing NSCLC angiogenesis.  相似文献   
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《Acta histochemica》2022,124(6):151931
ObjectiveTo investigate the role of exosomal miRNA-133 secreted by cardiac fibroblasts (CFs) in promoting cardiomyocyte differentiation.MethodsNeonatal rat CFs were cultured in vitro, and the cultured CFs were divided into three groups as follows: induction, miRNA-133 high expression, and miRNA-133 inhibition. miRNA-133 was transfected into CFs with lentivirus as a vector. CFs were transfected with the miRNA-133 inhibitor, and the markers of cardiomyocyte were detected through immunofluorescence staining, Western blotting, and real-time quantitative polymerase chain reaction (qRT-PCR) at 3, 8, and 14 days, respectively. The expression levels of cardiac troponin T (cTnT) and cardiac actin (α-actin) were determined, and qRT-PCR was used to detect the expression of miRNA-133 in the fibroblast exosomes.ResultsCFs subjected to immunofluorescence staining expressed vimentin and discoid domain receptor 2. The exosomes secreted by CFs were observed as small vesicles of 30–100 nm via transmission electron microscopy, and Western blotting was used to detect exosome-specific protein CD63 and CD9 expression. The expression levels of cTnT, α-actin, and exosomal miRNA-133 secreted into the supernatant of the miRNA-133 high-expression group increased gradually at different time points and reached the highest level at 14 days. The expression levels of cTnT, α-actin, and exosome miRNA-133 in the miRNA-133 inhibition group were the lowest.ConclusionThe exosomal miRNA-133, which is derived from CFs, can promote the differentiation of fibroblasts into cardiomyocyte-like cells.  相似文献   
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刘瑾  杨宗统  隋在云  杨青 《药学研究》2021,40(2):71-73,93
目的研究复方丹皮酚纳米乳对裸鼠体内人源肺癌A549的影响及部分机制研究。方法建立裸鼠人源肺癌A549移植瘤模型,灌胃给予不同剂量的复方丹皮酚纳米乳(48、96和192 mg·kg-1),观察其对A549移植瘤的治疗作用,每5 d使用游标卡尺测量裸鼠移植瘤的最长径和最短径,动态观察裸鼠移植瘤的生长情况,并计算其体积,以此绘出裸鼠移植瘤生长曲线。通过酶联免疫吸附法测定血清中白细胞介素2(interleukin-2,IL-2)和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)的水平,初步探讨其作用机制。结果所有治疗组均对裸鼠A549移植瘤肿瘤体积、肿瘤体积增长率有一定的抑制作用,且随剂量的增加,抑制作用更强;与荷瘤对照组比较,复方丹皮酚纳米乳高剂量组和康莱特注射液组血清白细胞介素2表达明显升高(P<0.01、P<0.01),复方丹皮酚纳米乳中、高剂量组和康莱特注射液组肿瘤坏死因子α表达水平明显升高(P<0.05、P<0.01、P<0.01)。结论复方丹皮酚纳米乳对人源肺癌A549裸鼠移植瘤具有一定的抑制作用,其作用机制可能与促进细胞因子白细胞介素2和肿瘤坏死因子α的表达有关。  相似文献   
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Reactivation of the p53 cell apoptosis pathway through inhibition of the p53-hDM2 interaction is a viable approach to suppress tumor growth in many human cancers and stabilization of the helical structure of synthetic p53 analogs via a hydrocarbon cross-link (staple) has been found to lead to increased potency and inhibition of protein–protein binding (J. Am. Chem. Soc. 129: 5298). However, details of the structure and dynamic stability of the stapled peptides are not well understood. Here, we use extensive all-atom molecular dynamics simulations to study a series of stapled α-helical peptides over a range of temperatures in solution. The peptides are found to exhibit substantial variations in predicted α-helical propensities that are in good agreement with the experimental observations. In addition, we find significant variation in local structural flexibility of the peptides with the position of the linker, which appears to be more closely related to the observed differences in activity than the absolute α-helical stability. These simulations provide new insights into the design of α-helical stapled peptides and the development of potent inhibitors of α-helical protein–protein interfaces.  相似文献   
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Aim: Previous studies have shown that exercise training reduced white adipose tissue (WAT) mass compared to that in sedentary controls, and that the smaller mass contained fewer adipocytes. However, the effect of exercise training on adipogenesis is not completely clear. Therefore, we re-examined the effect of exercise training on adipocyte numbers in WAT and, if such an effect was found tested the adipogenic responses of stromal-vascular fraction (SVF) cells containing adipose tissue-derived stem cells (ADSC) in epididymal WAT from exercise-trained (TR) rats. Methods: Wistar male rats were divided into two groups: control (C) and TR. The TR rats were subjected to exercise on a treadmill for 9 weeks. SVF cells containing ADSC were separated from epididymal WAT by centrifugation. Expression of adipocyte differentiation-related genes and adipogenesis of SVF cells were examined. Results: In SVF cells of TR rats, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and that of PPARγ target lipogenic genes was dramatically downregulated, whereas that of preadipocyte factor-1 gene was significantly upregulated. Lipid accumulation in SVF cells of TR rats after the induction of adipocyte differentiation was significantly suppressed in comparison with that of C rats. Moreover, increased expression of hypoxia-inducible factor-1α (HIF-1α) protein was observed in SVF cells of TR rats. Pre-treatment of YC-1, a potent HIF-1α inhibitor, in SVF cells of TR rats restored adipogenesis. Conclusion: These results suggest that exercise training suppresses the ability of SVF cells to differentiate into adipocytes, and that underlying mechanisms involve the upregulation of HIF-1α expression.  相似文献   
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A new triterpenoid saponin named clematichinenoside AR2, along with the six known compounds, was isolated and characterized from Clematis chinensis Osbeck (Ranunculaceae), a commonly used traditional Chinese medicine with anti-inflammatory and anti-rheumatoid activities. The structure of the new saponin was elucidated as 3-O-β-[(O-α-l-rhamnopyranosyl-(1 → 6)-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-ribopyranosyl-(1 → 3)-O-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)oxy]olean-12-en-21α-hydroxy-28-oic acid-O-α-l-rhamnopyranosyl-(1 → 4)-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl ester (1) by spectral analysis and chemical methods. The effects of two major saponins (clematichinenosides AR and AR2) on the secretion of TNF-α in murine peritoneal macrophages induced by lipopolysaccharides were further investigated. The result indicated that a majority of triterpenoid saponins of this herb may be useful in the exploration of lead compounds for the treatment of some autoimmune diseases.  相似文献   
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BackgroundInflammatory bowel disease (IBD) is a chronic inflammatory condition of gastrointestinal tract of immune, genetic and environmental origin. In the present study, we examined the effect of sesamol (SES), the main anti-oxidative constituent of Sesamum indicum (sesame seed) Linn. in the dinitrochlorobenzene (DNCB)-induced model for IBD in rats.MethodsThe groups were divided into normal control, DNCB control, SES and sulfasalazine (SS). On day 24, the rats were killed, colon removed and the macroscopic, biochemical and histopathological evaluations were performed.ResultsThe levels of MPO, TBARS and nitrite increased significantly (p < 0.05) in the DNCB group, whereas reduced significantly in the SES, SS treated groups. Serum nitrite levels were found to be insignificant between the different groups. IL-6 and TNF-α levels were significantly high in the DNCB group.ConclusionsWe conclude the mucosal protective effect of SES on colon due to its potent antioxidant actions. Further investigation is required in a chronic model of different rodent strain for its role involved in the cytokine pathway.  相似文献   
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