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81.
Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors. 相似文献
82.
Takuto Terashi Shotaro Otsuka Seiya Takada Kazuki Nakanishi Koki Ueda Megumi Sumizono 《Neurological research》2013,35(6):510-518
ABSTRACTObjective: Preconditioning exercise can exert neuroprotective effects after stroke; however, the effects of exercise intensity, frequency, duration are unknown. We investigated the neuroprotective effect of different frequency preconditioning exercise on neuronal apoptosis after cerebral ischemia in rats.Methods: Rats were divided into the following five groups: 5 times a week of exercise (5/w-Ex) group, 3 times a week of exercise (3/w-Ex) group, once a week of exercise (1/w-Ex) group, no exercise (No-Ex) group, and intact control (control) group. Rats were made to run on a treadmill for 30 min per day at a speed of 25 m/min for 3 weeks. After the running program, the rats were subjected to 60-min left middle cerebral artery occlusion. Two days after ischemia, the cerebral infarct volume, neurological and motor function, Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, expression of caspase-3, and TUNEL positive cells were examined in the cerebral cortex surrounding the ischemic zone.Results: The 3/w-Ex and 5/w-Ex groups showed significantly reduced infarct volumes compared with the No-Ex group, but the 1/w-Ex group did not. In addition, the 3/w-Ex and 5/w-Ex groups had improved neurological scores and sensorimotor function compared with the No-Ex group. The Bax/Bcl-2 ratio, expression of caspase-3, and TUNEL-positive cells significantly decreased in the penumbra area in the 3/w-Ex or 5/w-Ex groups compared with the No-Ex group.Discussion: Our findings suggested that three times or more per week of high-intensity preconditioning exercise exert neuroprotective effects through the downregulation of the Bax/Bcl-2 ratio and caspase-3 activation after stroke.Abbreviations: TUNEL: terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick and labeling; MCAO:middle cerebral artery occlusion; BAX:Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; TTC: 2,3,5-triphenyltetrazorlium chloride 相似文献
83.
Smitha Krishna Infante Andres F. Oberhauser J. Regino Perez‐Polo 《Journal of neuroscience research》2013,91(9):1152-1164
Neonatal hypoxia–ischemia (HI) is a common occurrence in preterm and low‐birth‐weight infants, and the incidence of low‐birth‐weight and preterm births is increasing. Characterization of brain injury after HI is of critical importance in developing new treatments that more accurately target the injury. After severe HI, neuronal cells undergo necrosis and secondary apoptosis of the surrounding cells as a result of neuroinflammation. We sought to characterize the biochemical pathways associated with cell death after HI. Bax, a cell death signaling protein, is activated after HI and translocates to the nucleus, endoplasmic reticulum, and mitochondria. The translocation patterns of Bax affect the resultant cell death phenotype (necrotic or apoptotic) observed. Although Bax is known to oligomerize once it is activated, less is known about the factors that control its translocation and oligomerization. We hypothesize that Bax kinase‐specific phosphorylation determines its oligomerization and intracellular localization. Using well‐established in vivo and in vitro models of neonatal HI, we characterized Bax oligomerization and multiorganelle translocation. We found that HI‐dependent phosphorylation of Bax determines its oligomerization status and multiorganelle localization, and, ultimately, the cell death phenotype observed. Understanding the mechanisms of Bax translocation will aid in the rational design of therapeutic strategies that decrease the trauma resulting from HI‐associated inflammation. © 2013 Wiley Periodicals, Inc. 相似文献
84.
目的 通过研究雷替曲塞抑制裸鼠MGC-803胃癌移植瘤的生长,初步探讨其相关作用机制。方法 建立人胃癌裸鼠皮下移植瘤模型,把24只裸鼠随机分为3 组,每组8只。对照组(生理盐水),低剂量组(雷替曲塞5 mg/kg),高剂量组(雷替曲塞12 mg/kg)。每周经腹腔注射给药2次,持续2周。详细记录裸鼠精神状态、体重以及肿瘤生长情况,免疫组化法检测裸鼠肿瘤组织Ki67及PCNA蛋白表达,并通过Western blottting法检测裸鼠肿瘤组织Caspase-3及Bax蛋白表达。结果 治疗期间雷替曲塞低剂量组和高剂量组裸鼠体重均低于对照组,低剂量组、高剂量组的抑瘤率分别为27.54%、44.20%,差异有统计学意义(P<0.05);免疫组化法显示低剂量组、高剂量组Ki67阳性细胞率分别为58.95%、42.16%,PCNA阳性细胞率分别为51.36%、37.27%,均明显低于对照组(P<0.05);Western blotting法表明低剂量组、高剂量组Caspase-3和Bax蛋白表达均明显高于对照组(P<0.05)。结论 雷替曲塞可抑制人胃癌裸鼠移植瘤的生长增殖,其机制可能与提高Caspase-3和Bax蛋白表达、从而促进细胞凋亡有关。 相似文献
85.
目的:通过观察参附注射对脓毒症大鼠心肌细胞凋亡及Bcl-2、Bax蛋白表达的影响,阐明参附注射液抗脓毒症心肌损伤的相关机制。方法:雄性SD大鼠随机分为3组:假手术组、模型组和参附组,每组8只。以盲肠结扎穿孔(Cecal Ligation and Puncture,CLP)法建立脓毒症大鼠动物模型,观察各组大鼠心肌酶谱变化;凋亡原位末端标记法(TUNEL) 检测心肌细胞凋亡指数,RT-PCR 法检测心肌细胞Bcl-2 mRNA、Bax mRNA表达。结果:参附组大鼠心肌酶谱升高程度较模型组低(P<0.05),模型组较假手术组心肌酶水平高(P<0.05);参附组大鼠心肌细胞TUNEL评分平均光密度(MOD)较模型组明显降低(P<0.05),模型组较假手术组升高(P<0.05);参附组大鼠心肌细胞Bcl-2 mRNA表达较其他两组均升高(P<0.05),而Bax mRNA表达较其他两组降低(P<0.05)。结论:参附注射液能减轻脓毒症大鼠的心肌损伤,其作用机制与上调Bcl-2 mRNA的表达,下调Bax mRNA表达,减少心肌细胞凋亡相关。 相似文献
86.
Objective To investigate the effects of norcantharidin on the proliferation and apoptosis related proteins
Bax and Bcl-2 of human melanoma M14 cells. Methods Melanoma M14 cell line cultured in vitro was treated with
concentrations of 50, 100 and 500 μg / L norcantharidin respectively, and untreated cells were used as control. Cell proliferation was detected by CCK-8 method after treatment for 24 h and 48 h. Morphology of cells was observed under inverted microscope. DAPI nuclear staining was used to observe the morphological changes of apoptosis under fluorescence microscope. The expressions of Bax and Bcl-2 were detected by Western blot assay. Results CCK-8 results showed that concentrations of 100 and 500 μg/L norcantharidin inhibited the proliferation of melanoma M14 cells after treatment for 24 h and 48 h (P<0.05), and the higher the concentration, the more significant the inhibitory effect. The cells showed irregular contours, nucleus shrinkage, small volume, and poor cell adhesion of apoptosis changes under inverted microscope and
fluorescence microscope. Western blot analysis showed that the relative expression of Bcl-2 decreased gradually with the increased concentration of norcantharidin (P<0.05), and the relative expression of Bax increased gradually (P<0.05).Conclusion Norcantharidin can inhibit the proliferation of melanoma M14 cells, and its mechanism may be related to the promotion of apoptosis. 相似文献
87.
Tetrandrine, a constituent of Chinese herb Stephania tetrandra, causes cell death in prostate cancer, but the molecular mechanisms leading to apoptosis is not known. Here we demonstrated that tetrandrine selectively inhibits the growth of prostate cancer PC3 and DU145 cells compared to normal prostate epithelial PWR-1E cells. Tetrandrine-induced cell death in prostate cancer cells is caused by reactive oxygen species (ROS)-mediated activation of c-Jun NH2-terminal kinase (JNK1/2). JNK1/2-mediated proteasomal degradation of c-FLIPL/S and Bcl2 proteins are key events in the sensitization of prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Tetrandrine-induced JNK1/2 activation caused the translocation of Bax to mitochondria by disrupting its association with Bcl2 which was accompanied by collapse of mitochondrial membrane potential (MMP), cytosolic release of cytochrome c and Smac, and apoptotic cell death. Additionally, tetrandrine-induced JNK1/2 activation increased the phosphorylation of Bcl2 at Ser70 and facilitated its degradation via the ubiquitin-mediated proteasomal pathway. In parallel, tetrandrine-mediated ROS generation also caused the induction of ligand-independent Fas-mediated apoptosis by activating procaspase-8 and Bid cleavage. Inhibition of procaspase-8 activation attenuated the cleavage of Bid, loss of MMP and caspase-3 activation suggest that tetrandrine-induced Fas-mediated apoptosis is associated with the mitochondrial pathway. Furthermore, most of the signaling effects of tetrandrine on apoptosis were significantly attenuated in the presence of antioxidant N-acetyl-l-cysteine, thereby confirming the involvement of ROS in these events. In conclusion, the results of the present study indicate that tetrandrine-induced apoptosis in prostate cancer cells is initiated by ROS generation and that both intrinsic and extrinsic pathway contributes to cell death. 相似文献
88.
Iso-suillin, an isomer of suillin that belongs to the prenylphenol class of fungal derivatives, was isolated from petroleum ether extracts of Suillus flavus. The IC50 value of iso-suillin in K562 cells was 0.87 μM, which was lower than the positive control cisplatin (19.33 μM). Iso-suillin-treated K562 cells exhibited an increased rate of apoptosis, mitochondrial membrane potential (MMP) depolarization, and G0/G1 arrest. Western blot analysis revealed that these cells displayed significantly upregulated expression of several apoptosis-related proteins, including cytochrome c, caspase 9, FADD (Fas-associating protein with a novel death domain), caspase 8, caspase 3, and Bax. Moreover, the expression of two anti-apoptosis proteins, NF-κB and Bcl-2, was downregulated. Inhibitors of caspase 9 and caspase 8 protected the K562 cells from apoptosis. Taken together, our results suggest that iso-suillin induces K562 apoptosis through the mitochondrial and death receptor pathways and that iso-suillin may represent a candidate anti-leukemia treatment. 相似文献
89.
目的:研究凋亡调控蛋白Bcl-2和Bax在正常早孕与稽留流产绒毛组织结构中的表达及其意义,探讨稽留流产原因。方法选择本院就诊的稽留流产患者和早孕人工流产患者各60例,分为A组、B组。流产后立即留取胚胎绒毛组织送病理。分别应用光镜观察各组绒毛组织细胞形态结构的改变;同时应用免疫组织化学方法和计算机图文分析系统检测Bax、Bcl-2在各组绒毛的表达及细胞凋亡情况。结果稽留流产组绒毛滋养细胞中凋亡指数为(33.32±0.79)%,明显高于对照组B组的(18.90±0.63)%,差异有统计学意义(P〈0.01)。Bax和Bcl-2在两组合体滋养细胞中的阳性率比较显示,稽留流产组中Bax阳性率增高, Bcl-2阳性率下降, Bcl-2/Bax比值降低,差异均有统计学意义(P〈0.01)。结论蜕膜绒毛中Bax阳性率增高和Bcl-2阳性率下降可使绒毛合体滋养细胞凋亡明显增加,并进一步导致稽留流产发生。 相似文献
90.
Yuan Liu ;Yueling Zhang ;Zhaohui Gu ;Lina Hao ;Juan Du ;Qian Yang ;Suping Li ;Liying Wang ;Shilei Gong 《中国神经再生研究》2014,9(14):1402-1408
Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspase-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite. 相似文献