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1.
目的 对3例怀疑M蛋白相关性杆状体肌病患者进行肌肉病理检查、M蛋白筛查明确诊断,提高对这一罕见疾病的认识并探讨对此疾病的诊疗方案。 方法 报道3例M蛋白相关性杆状体肌病,结合文献复习对病例特点进行总结。 结果 3例患者均表现为进行性加重的肌肉无力症状,完善肌肉活检诊断为杆状体肌病,合并M蛋白,给予行自体造血干细胞移植治疗有效。 结论 散发的晚发型成人杆状体肌病是一种罕见的、亚急性进展的肌病,常合并M蛋白,针对清除M蛋白的治疗是有效的。 相似文献
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Since their inception in the 1960s–70s, mesenchymal stem/stromal cells (MSCs) have gained interest because of their differentiation potential, anti-inflammatory effects, and immune-modulating properties. Both cell-based and cell-free MSC treatments show healing capacity in injured tissues. Cell-based treatment comprises MSCs and all secreted products, whereas cell-free treatments include only the secreted products. MSCs are therapeutically administered to many damaged organs owing to their efficacy. Specifically, the eye is a unique organ system to study the effects of MSCs, as treatment is easily applied and measured owing to its external location. The eye holds an immune-privileged status, wherein inflammation and immune responses are innately down-regulated. As excessive inflammation in the cornea often leads to fibrosis and irreversible corneal hazing, many studies have investigated the anti-inflammatory and immune-modulating capacities of MSCs. Decades of research suggest that MSCs modulate the immune response by secreting cytokines, growth factors, and extracellular matrix proteins that inhibit the infiltration of inflammatory cells following injury and promote a healing phenotype via M2 macrophage polarization. MSCs have also shown trans-differentiation potential into cornea-specific cell types during the wound healing process, such as corneal epithelial, stromal, or endothelial cells. This review discusses recent investigations of MSC treatment in the cornea, focusing on therapeutic efficacy, mechanisms, and future directions. 相似文献
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Qi Zhang Shuang Wu Qianqian Xiao Chenping Kang Hong Hu Xiaohong Hou Xuetao Wei Weidong Hao 《Journal of applied toxicology : JAT》2022,42(4):588-599
Obesogens are a subset of endocrine disruptor chemicals (EDCs) that cause obesity. The typical EDC 4-nonylphenol (4-NP) has been identified as an obesogen. However, the in vitro effects of 4-NP on adipogenesis remain unclear. In this study, 3T3-L1 preadipocytes and C3H/10T1/2 mesenchymal stem cells (MSCs) were used to investigate the influence of 4-NP on adipogenesis. The differentiation protocols for 3T3-L1 preadipocytes and C3H/10T1/2 MSCs took 8 and 12 days, respectively, beginning at Day 0. In differentiated 3T3-L1 preadipocytes, 20 μM 4-NP decreased cell viability on Days 4 and 8. Exposure to 4-NP inhibited triglyceride (TG) accumulation and adipogenic marker expression on Days 0–8, but the inhibitory effects were weaker on Days 2–8. The protein expression of pSTAT3 or STAT3 decreased on Days 0–8 and 2–8. Conversely, 4-NP promoted TG accumulation and the adipogenic marker expression in C3H/10T1/2 adipocytes. The opposing effects were attributed to physiological differences between the two cell lines. The 3T3-L1 preadipocytes are dependent on mitotic clonal expansion (MCE) to drive differentiation, while C3H/10T1/2MSCs and human preadipocytes are not. Additionally, 4-NP downregulated β-catenin expression in C3H/10T1/2 adipocytes. Accordingly, we hypothesized that 4-NP promotes adipogenesis. The role of the canonical Wnt pathway in the promotion of adipogenesis by 4-NP requires further validation. This study provides new insights into the mechanisms and appropriate risk management of 4-NP. 相似文献
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《Immunobiology》2022,227(3):152211
ObjectiveThe present study was intended to investigate the role of embryonic stem cell-derived exosomes (ESC-Exos) in Müller cell retrodifferentiation and their specific mechanism.MethodsFollowing co-incubation of the extracted ESC-Exos and Müller cells, their effects on the retrodifferentiation and proliferation of Müller cells were measured by EdU staining, immunofluorescence, and western blot. ESCs transfected with small interfering RNA of BDNF were co-incubated with Müller cells to determine Müller cell proliferation and retrodifferentiation. β-catenin expression in the nucleus and GSK-3β phosphorylation were measured to determine the role of the Wnt pathway in Müller cells. The function of the retina in RCS rats was observed using flash electroretinogram.ResultsCo-incubation of ESCs with Müller cells or overexpression of BDNF contributed to Müller cell retrodifferentiation and proliferation, as evidenced by increased cell proliferation, fluorescence intensities of proliferation markers and retinal stem cell markers, and expression of BDNF and β-catenin, and suppressed GSK-3β phosphorylation. However, co-incubation with ESCs silencing BDNF or treatment with GW4869 inhibited the proliferation and retrodifferentiation of retinal Müller cells. In addition, exosome injection increased BDNF, BrdU, PH3, SOX2, and Pax6 expression, enhanced β-catenin expression in the nucleus, diminished GSK-3β, and improved retinal degeneration in RCS rats.ConclusionESC-Exos accelerated Müller cell retrodifferentiation and proliferation through Wnt pathway activation by delivering BDNF protein to Müller cells. 相似文献
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目的:比较脑转移立体定向放射外科中共面与非共面模式下剂量学差异,对单组非共面模式在脑转移立 体定向放射外科中的应用进行可行性分析。方法:回顾性分析 14例脑转移患者,采用容积旋转调强放疗与无均整块 技术技术,处方剂量 25Gy,在计划设计中用共面弧、单组非共面弧、多组非共面弧 3种模式,比较 3种模式下靶区剂 量、适形指数(conformityIndex,CI)、梯度指数(gradientindex,GI)和脑组织受量以及出束时间、执行效率等差别。 结果:共面计划无论相对于单组非共面计划还是多组非共面计划而言,出束时间以及 CI差异均无统计学意义(P> 0.05)。3种模式都能达到临床要求,但剂量分布上差异有统计学意义。共面计划中 GI(GI50 =4.84±0.52,GI25 = 16.13±2.73),要远远高于单组非共面计划 GI(GI50=3.66±0.44,GI25=9.94±1.41)(P<0.001,P<0.001)和多组 非共面计划 GI(GI50=3.73±0.42,GI25=9.32±1.23)(P<0.001,P<0.001),同时脑组织受量(V10 =11.46±3.47, V5=35.25±11.79)要高于单组非共面计划(V10=10.44±3.16,V5=28.55±9.62)(P<0.001,P<0.001)和多组非 共面计划(V10=10.61±3.4,V5=25.37±904)(P<0.001,P<0.001)。单组非共面与多组非共面计划比较而言, 照射时间和 CI以及 GI50差异无统计学意义(P>0.05)。多组非共面计划在低剂量区域能实现更快的剂量跌落,脑 组织受量中低剂量体积 V5要小于单组非共面计划。结论:共面计划在不增加出束时间的前提下,能实现和非共面 计划类似的处方剂量分布,同时整个流程时间最短,执行效率最高,但是非共面计划可以实现更快速的靶区外剂量 跌落,更好地保护脑组织。单组非共面与多组非共面计划质量相近,多组非共面计划在低剂量区域存在着一定的优势。单组非共面计划整个流程照射时间短,执行效率高,在临床中可以优先考虑使用单组非共面模式。 相似文献
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胶质淋巴系统是一个主要由星形胶质细胞水通道蛋白4介导的依靠动脉、静脉周围血管间隙的脑脊液-脑组织液交换流动的系统,是阿尔茨海默病、脑卒中、帕金森病、失眠、抑郁症等脑病的共同特征,是一条新的脑代谢途径,可以清除包括β-淀粉样蛋白、乳酸在内的代谢产物。本文综合分析了全球有关胶质淋巴系统在脑部疾病的研究,得出:胶质淋巴系统可能为神经退行性疾病等发病机制和诊治策略研究带来新视角;胶质淋巴系统有望为一些脑部疾病诊断提供新的有效证据;胶质淋巴系统可能是脑部疾病治疗给药方式的新途径。 相似文献
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Cancer Stem Cells as a Prognostic Biomarker and Therapeutic Target Using Curcumin/ Piperine Extract for Multiple Myeloma 下载免费PDF全文
Sara A MekkawyMohga S AbdallaMohamed M OmranNaglaa M HassanRaafat AbdelfattahIbrahim M. Abdel-Salam 《Asian Pacific journal of cancer prevention》2022,23(10):3507-3515
Background: Multiple myeloma (MM) is a hematological bone marrow malignancy that can be treated but is usually fatal. Medication resistance is the major cause of relapses due to cancer stem cells (CSCs). As a result, this study aimed to identify multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of twelve MM patients with pathological complete response (pCR) after chemotherapy and to investigate the potential effect of Curcumin/Piperine (C/P) extract as an anti-MMCSCs treatment in twenty newly diagnosed patients. Methods: This study included twenty bone marrow (BM) samples from newly diagnosed MM patients and twelve BM samples from pCR patients after a year of treatment. The MTT test was performed to assess the treatment’s effective dosage. A flow cytometer was used to identify MMCSCs, cell cycle profile, extract’s apoptotic activity, and proliferation marker in the selected samples. Also, a colony formation test and stemness protein were investigated. Results: In newly diagnosed MM patients, the C/P extract suppressed MMCSCs by 64.71% for CD138-/CD19- and 38.31% for CD38++. In MM patients’ samples obtained after one year of treatment, the MMCSCs inhibition percentage reached 44.71% (P < 0.008) for CD138-/CD19- and 36.94% (P < 0.221) for CD38++. According to cell cycle analyses, the number of cells treated with C/P extract was significantly reduced in the S and G0/G1 phases (87.38%: 35.15%, and 4.83%: 2.17% respectively), with a rapid increase in the G2/M phases (1.1%: 2.2%.). MMCSCs apoptosis was identified using a flow cytometer and Annexin-V. Multiple myeloma stem cell (MMCSC) proliferation was inhibited. Clonogenicity was suppressed by 60%, and stemness protein expression was reduced by 70%. Conclusion: MMCSCs in the bone marrow of MM-pCR patients can be utilized as a prognostic tool to predict recurrent multiple myeloma incidence. Also, the therapeutic potential of C/P extract as a prospective anti-MM drug targeting MMCSCs. 相似文献