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121.
目的 研究共表达m-bcr/abl融合基因转录子对初诊慢性髓系白血病(CML)患者的巨核细胞形态的影响.方法 分别用逆转录-聚合酶链反应(RT-PCR)和巢式PCR检测M和m-bcr/abl融合基因转录子.盲法计数患者骨髓涂片1.0 cm×1.5 cm2面积内巨核细胞数,随机选取20个巨核细胞分类计数并测定成熟期巨核细胞直径;计数产板型巨核细胞产血小板数.结果 107例初诊CML患者M和m-bcr/abl共表达者56例,b3a2型31例,b2a2型25例.共表达m-bcr/abl的b3a2型初诊CML患者血小板数比单表达M-bcr/abl和b2a2型m-bcr/abl( )患者高(P<0.05).对巨核细胞形态观察,在b3a2和b2a2组,共表达m-bcr/abl和单表达M-bcr/abl的患者骨髓1.0 cm×1.5 cm面积内巨核细胞数、成熟巨核细胞数和直径差异均无统计学意义(P>0.05);共表达m-bcr/abl的b3a2型患者产板型巨核细胞产板数比单表达M-bcr/abl患者高(P<0.05);而b2a2型的共表达m-bcr/abl组和单表达M-bcr/abl组1.0 cm × 1.5 cm面积内巨核细胞数、成熟巨核细胞数和直径及产板型巨核细胞产板数差异均无统计学意义(P>0.05).结论 共表达m-bcr/abl的b3a2型初诊CML患者血小板数增高是由其巨核细胞产板数多造成的,而与其巨核细胞数、产板型巨核细胞数和直径无关. 相似文献
122.
目的 探究硒化卡拉胶(KSC)联合阿霉素(ADR)对肝癌耐药细胞HepG-2/ADR的协同抗肿瘤效应及其逆转作用机制。方法 MTT法分别检测HepG-2/ADR耐药细胞对阿霉素、顺铂(DDP)、紫杉醇(TAX)3种化疗药物的多药耐药性,并判断KSC对HepG-2/ADR耐药细胞的逆转作用;流式细胞术检测KSC和ADR对HepG-2/ADR耐药细胞周期和细胞凋亡的影响;Western blot检测KSC和ADR对HepG-2/ADR细胞中耐药相关蛋白、细胞周期和细胞凋亡蛋白的影响。RT-qPCR进一步验证HepG-2/ADR细胞中耐药相关基因的表达。结果 MTT结果显示,HepG-2/ADR耐药细胞对ADR、TAX、DDP均具有耐药性,且KSC具有逆转肝癌HepG-2/ADR细胞多药耐药性的作用,两药联合表现为相加作用。流式细胞术表明KSC和ADR均可诱导HepG-2/ADR细胞发生凋亡和S期周期阻滞。Western blot结果显示,KSC和ADR显著下调耐药蛋白P-gp、MRP1、ABCG2以及细胞周期蛋白Cyclin A、Cyclin E、CDK2、Survivin和抑凋亡因子Bcl-2的表达(P<0.05或P<0.01),显著上调促凋亡蛋白Bax、Caspase-3、Caspase-9、Cleaved-Caspase-3和Cleaved-Caspase-9的表达(P<0.05或P<0.01);联合组可协同促进或抑制细胞凋亡和细胞周期相关蛋白的表达。RT-qPCR表明KSC和ADR单独及联合均能显著下调P-gp1、MRP1和ABCG2耐药基因的表达。结论 KSC可有效逆转肝癌多药耐药性,协同提高HepG-2/ADR细胞对阿霉素的化疗敏感性,其机制可能与诱导细胞凋亡与细胞周期阻滞有关,通过下调多药耐药相关蛋白P-gp、MDR1和ABCG2的表达,进而逆转肝癌多药耐药性。 相似文献
123.
YouYou Lv Han Wang HaiTing Fan Ting Xu WenJun Xin RuiXian Guo 《CNS Neuroscience & Therapeutics》2022,28(8):1259
AimsPotassium (K+) channels have been demonstrated to play a prominent involvement in nociceptive processing. Kir7.1, the newest members of the Kir channel family, has not been extensively studied in the CNS, and its function remains largely unknown. The present study investigated the role of spinal Kir7.1 in the development of pathological pain.Methods and ResultsNeuropathic pain was induced by spared nerve injury (SNI). The mechanical sensitivity was assessed by von Frey test. Immunofluorescence staining assay revealed that Kir7.1 was predominantly expressed in spinal neurons but not astrocytes or microglia in normal rats. Western blot results showed that SNI markedly decreased the total and membrane expression of Kir7.1 in the spinal dorsal horn accompanied by mechanical hypersensitivity. Blocking Kir7.1 with the specific antagonist ML418 or knockdown kir7.1 by siRNA led to mechanical allodynia. Co‐IP results showed that the spinal kir7.1 channels were decorated by SUMO‐1 but not SUMO‐2/3, and Kir7.1 SUMOylation was upregulated following SNI. Moreover, inhibited SUMOylation by GA (E1 inhibitor) or 2‐D08 (UBC9 inhibitor) can increase the spinal surface Kir7.1 expression.ConclusionSUMOylation of the Kir7.1 in the spinal cord might contribute to the development of SNI‐induced mechanical allodynia by decreasing the Kir7.1 surface expression in rats. 相似文献
124.
目的:探索学习投入、专业承诺对农村订单定向医学生核心能力的影响,为提升基层卫生人才队伍的质量提供理论参考。方法:通过多阶段整群抽样方法,抽取S省两所医学院校的520名农村订单定向医学生作为研究对象进行调查。采用分层回归法分析学习投入对农村订单定向医学生核心能力的影响,简单斜率检验分析专业承诺对前述两者关系的调节效应。结果:S省农村订单定向医学生核心能力总体平均得分为(3.39±0.549);学习投入对农村订单定向医学生核心能力存在显著正向影响(β=0.358),且专业承诺对前述两者关系存在调节效应,该调节效应使得学习投入对核心能力的影响变强(β=0.206)。结论:完善农村订单定向医学生培养政策,严把录取质量,加大基层基地的建设与投入,重视学生职业素质教育,提升核心能力。 相似文献
125.
YanTing Zhou YuQing Yu Hui Yang Han Yang YanFei Huo Yang Huang XinXia Tian WeiGang Fang 《Cancer science》2022,113(7):2457
Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple‐negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2––YAP‐CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM‐1 on ECs. Both apyrase (ATP‐diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy. 相似文献
126.
Boyi Niu Yixian Zhou Kaixin Liao Ting Wen Sixian Lao Guilan Quan Xin Pan Chuanbin Wu 《药学学报(英文版)》2022,12(4):2074
The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.KEY WORDS: Cancer therapy, Cisplatin, Drug resistance, Glutathione depletion, Glutathione S-transferases, Disulfide bonds, Organosilica hybrid nanoparticles, Ethacrynic acid 相似文献
127.
目的探讨急性高原缺氧条件下氰化钠中毒对大鼠脑组织能量代谢的影响。方法雄性sD大鼠,分为平原组和高原组。平原组动物在本地常规实验室内处理。高原组动物放置于模拟4000m海拔高度的低压舱内3d后开始实验。为大鼠腹腔注射氰化钠(NaCN)3.6mg/kg染毒,于0、0.5、1、2、4、6h6个时相点麻醉后断头取脑。以干湿质量法测定脑组织含水量,伊文思蓝法检测脑组织血管通透性,高效液相色谱(high performance liquid chromatography,HPLC)法测定大鼠脑纹状体和海马组织腺苷三磷酸(adenosine triphosphate,ATP)、腺苷二磷酸(adenosine diphosphate,ADP)和腺苷-磷酸(adenosine monophosphate,AMP)含量。结果与平原组比较,高原缺氧环境氰化钠中毒大鼠脑组织含水量增加,纹状体和海马组织ATP和ADP含量减少,AMP含量增加。结论高原缺氧可导致大鼠脑组织腺苷酸能量代谢障碍,缺氧条件下氰化钠中毒可进一步加重脑组织能量代谢障碍,同时脑水肿也进一步加重。 相似文献
128.
针刺镇痛在临床上被广泛应用。针刺的神经传导通路与机体痛觉传导通路基本相似,对周围神经和中枢神经均有一定的影响,因此推断这可能是针刺缓解疼痛的一种调节机制。本文总结了近五年针刺治疗各种疼痛疾病的机制研究,从传导通路上分析得知针刺能激发神经元活性,改善周围神经的病理变化,增加神经元之间突触传递,修复受损的周围神经以缓解疼痛。此外,应用针刺或加用电针治疗痛症,能改善大脑内与疼痛相关各功能区之间的联系,对镇痛起到一定的中枢调控作用。在研究中还发现针刺能减少病变区炎性反应和细胞凋亡,增加细胞自噬和血管调节因子的表达。这些反应之间常存在一定的相互作用,共同缓解机体疼痛症状。然而,临床中针刺手法及辅助方法众多,治疗选取的相关穴位各异,根据疾病定位定性后选择最优组合方式是今后总结经验的重要目标。 相似文献
129.
Chengwei Xiang Zekun Yang Ting Xiong Ting Wang Jie Yang Mei Huang Dingxiang Liu Ruiai Chen 《Viruses》2022,14(7)
Avian interferon regulatory factors 1 and 7 (IRF1 and IRF7) play important roles in the host’s innate immunity against viral infection. Our previous study revealed that duck tembusu virus (DTMUV) infection of chicken fibroblasts (DF1) and duck embryo fibroblasts (DEFs) induced the expression of a variety of IFN-stimulated genes (ISGs), including VIPERIN, IFIT5, CMPK2, IRF1, and IRF7. IRF1 was further shown to play a significant role in regulating the up-expression of VIPERIN, IFIT5, and CMPK2 and inhibiting DTMUV replication. In this study, we confirm, through overexpression and knockout approaches, that both IRF1 and IRF7 inhibit DTMUV replication, mainly via regulation of type I IFN expression, as well as the induction of IRF1, VIPERIN, IFIT5, CMPK2, and MX1. In addition, IRF1 directly promoted the expression of VIPERIN and CMPK2 in an IFN-independent manner when IRF7 and type I IFN signaling were undermined. We also found that non-structural protein 2B (NS2B) of DTMUV was able to inhibit the induction of IFN-β mRNA triggered by Newcastle disease virus (NDV) infection or poly(I:C) treatment, revealing a strategy employed by DTMUV to evade host’s immunosurveillance. This study demonstrates that avian IRF7 and IRF1 play distinct roles in the regulation of type I IFN response during DTMUV infection. 相似文献
130.
目的研究乳腺癌基因诊断的准确率。方法用流式细胞光度分析技术对84例乳腺癌细胞 DNA、RNA含量进行定量分析。结果DNA异倍率为71.43%;RNA增高率为85.71%;用“标准DI”和“标准RI”为指标判断乳腺癌的准确率分别为78.57%和83.33%;且双指标同时应用时判断的准确率 92.86%,高于任一单指标。结论“标准DI”和“标准RI”是判断乳腺肿瘤良恶性生物学性质的理想指标。 相似文献