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951.
三氧化二砷对人肺腺癌细胞的细胞毒作用及其机制 总被引:7,自引:0,他引:7
背景与目的:三氧化二砷(arsenictrioxide,As2O3)应用于急性早幼粒细胞性白血病(acutepromyelocyticleukemia,APL)的临床化疗已显示较好疗效。目前,已开展了将As2O3用于治疗胃癌、头颈部癌和食管癌等实体瘤的实验研究。本研究旨在探讨As2O3对人肺腺癌SPCA1细胞的毒性及其作用机制。方法:MTT法检测As2O3对SPCA1细胞的生长抑制作用;流式细胞术测定经不同浓度As2O3处理后的SPCA1细胞的细胞周期改变、凋亡相关蛋白Fas和Bcl-2阳性细胞百分率及细胞内钙离子(IECa2+)含量变化。结果:As2O3可显著抑制SPCA1细胞生长增殖,且呈剂量-效应关系(r=0.973,P<0.05),其IC50为8.56μmol/L;As2O3能显著增加Fas蛋白表达和IECa2+含量(P<0.05),并使细胞周期阻滞在G2/M期,但对Bcl-2表达无影响(P>0.05)。结论:As2O3对SPCA1细胞有显著的毒性作用,其机制可能与上调Fas表达和增加IECa2+含量及阻滞细胞周期有关。 相似文献
952.
One new triterpene, kudinchalactone A (1), and four new triterpenoid saponins, ilekudinchosides A-D (2- 5), were isolated from the leaves of Ilex kudincha C.?J. Tseng along with eight known triterpenoids. These new compounds were elucidated by spectroscopic methods including 1D and 2D NMR, HR-TOF-MS, and CD spectra. Compounds 2, 3, 12, and 13 showed antibacterial activities against Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA). 相似文献
953.
Objectives Isoflurane preconditioning has been shown to protect endothelial cells against lipopolysaccharide and cytokine induced injury. This study was designed to determine whether isoflurane preconditioning increased endothelial cell tolerance to ischaemia. Methods Bovine pulmonary arterial endothelial cells were exposed or not exposed to various concentrations of isoflurane for 1 h. After a 30‐min isoflurane‐free period, cells were subjected to oxygen‐glucose deprivation (OGD) for 3 h and reoxygenation for 1 h. Lactate dehydrogenase release from cells was used to measure cell injury. In some experiments, various protein kinase C (PKC) inhibitors and ATP‐sensitive potassium channel (KATP channel) inhibitors were present from 30 min before isoflurane treatment to the end of isoflurane treatment. Key findings Isoflurane preconditioning dose‐dependently decreased the OGD induced lactate dehydrogenase release. This protection was inhibited by 2 µM chelerythrine, a general PKC inhibitor, or 10 µM Gö6976, an inhibitor for the conventional PKCs. This protection was also inhibited by 0.3 µM glybenclamide, a general KATP channel inhibitor, and 500 µM 5‐hydroxydecanoate, a mitochondrial KATP channel blocker. In addition, pretreatment with 100 µM diazoxide, a KATP channel activator, for 1 h also reduced OGD induced endothelial cell injury. This diazoxide induced protection was inhibited by chelerythrine. Conclusions The results suggest that isoflurane preconditioning induces endothelial protection against in‐vitro simulated ischemia. This protection may be mediated at least in part by conventional PKCs and mitochondrial KATP channels. The results also indicate that PKCs may be downstream of KATP channels in causing endothelial protection. 相似文献
954.
Zuo X Djordjevic JT Bijosono Oei J Desmarini D Schibeci SD Jolliffe KA Sorrell TC 《Molecular pharmacology》2011,80(3):476-485
Miltefosine has antifungal properties and potential for development as a therapeutic for invasive fungal infections. However, its mode of action in fungi is poorly understood. We demonstrate that miltefosine is rapidly incorporated into yeast, where it penetrates the mitochondrial inner membrane, disrupting mitochondrial membrane potential and leading to an apoptosis-like cell death. COX9, which encodes subunit VIIa of the cytochrome c oxidase (COX) complex in the electron transport chain of the mitochondrial membrane, was identified as a potential target of miltefosine from a genomic library screen of the model yeast Saccharomyces cerevisiae. When overexpressed in S. cerevisiae, COX9, but not COX7 or COX8, led to a miltefosine-resistant phenotype. The effect of miltefosine on COX activity was assessed in cells expressing different levels of COX9. Miltefosine inhibited COX activity in a dose-dependent manner in Cox9p-positive cells. This inhibition most likely contributed to the miltefosine-induced apoptosis-like cell death. 相似文献
955.
Radix Scutellariae is the dried root of the medicinal plant Scutellariae baicalensis Georgi. It exhibits a variety of therapeutic effects and has a long history of application in traditional formulations as well as in modern herbal medications. It has been confirmed that flavonoids are the most abundant constituents and induce these therapeutic effects. Six flavones are proven to be the major bioactive flavones in Radix Scutellariae existing in the forms of aglycones (baicalein, wogonin, oroxylin A) and glycosides (baicalin, wogonoside, oroxylin A-7-glucuronide). All six flavones are pharmacologically active and show great potential in the treatment of inflammation, cancers and virus-related diseases. The current review covers the preparation of the herb Radix Scutellariae, quantification of its major bioactive ingredients, and pharmacological effects of the proposed six bioactive flavones. In addition, this review summarizes the pharmacokinetic profiles of the bioactive flavones reported so far that could be used for further improvement of their pharmacokinetic study. Moreover, due to abundant co-occurring bioactive components in Radix Scutellariae, our review further documents the pharmacokinetic interactions among them. 相似文献
956.
957.
Baicalein (Ba) was found to be subject to serious first-pass metabolism after oral administration. We previously revealed the important role of intestine in the low oral bioavailability of Ba. The present study aims to evaluate the hepatic metabolism and disposition of Ba. Ba was given to Sprague-Dawley rats through bolus or infusion via intravenous or intra-portal route of administrations. Both plasma and bile samples at different time intervals were obtained. Concentrations of Ba and potential metabolites in the collected samples were analyzed with HPLC/UV and identified by LC/MS/MS, respectively. Plasma concentration versus time profiles of Ba obtained from intravenous and intra-portal administrations were compared to estimate the extent of hepatic metabolism. In addition, transport studies of baicalein-7-glucuronide (BG), one of the major metabolites of Ba, were carried out using transfected cell systems overexpressing various human organic anion-transporting polypeptide (OATP) isoforms to estimate the specific transporters involved in the hepatic disposition of Ba metabolites. The results showed that liver, in addition to intestine, also conferred extensive metabolism to Ba. Several mono- and di-conjugates of Ba, which were mainly glucuronides, sulfates, and methylates, were found in bile. The transport study demonstrated that besides MRPs and BCRP, human OATP2B1 and OATP1B3 in liver might also mediate the secretion of BG to bile. In summary, liver plays an important role in the metabolism of Ba and transport of its conjugated metabolites. 相似文献
958.
959.
目的通过对气相色谱法检测原料乳中农药残留量的测量过程不确定度来源的系统分析,提高对原料乳中农药残留量的检测水平和能力,并找出影响测量结果不确定度的主要因素;方法确立检测过程数学模型,用气相色谱法检测原料乳中有机磷农药残留量、对测量过程不确定度进行评价。结果原料乳中有机磷农药残留量的测量标准不确定度由称量、样品提取过程、稀释过程、标准物质、进样体积和仪器校准值引入的不确定度各组分合成。测量结果的扩展不确定度按式U=k×Cx×urel(合)计算。测定结果报告C=Cx±U,以加入农药标准物质至0.4mg/kg的原料乳做气相色谱法检测6种有机磷残留量分别报告为(0.4±0.050)mg/kg、(0.4±0.029)mg/kg、(0.4±0.027)mg/kg、(0.4±0.029)mg/kg、(0.4±0.057)mg/kg、(0.4±0.034)mg/kg。结论从气相色谱法检测原料乳中农药各组分残留量的测量不确定度分量汇总分析可以看出,测量不确定度一般来源于随机性和模糊性,是由许多分量组成,其分量可用统计分布来进行评价,并且以实验标准(偏)差表征。 相似文献
960.
Chinese medicine has been used to treat a variety of cancer-related conditions. This study aims to examine the prevalence and patterns of Chinese medicine usage by cancer patients. We reviewed articles written in English and found only the Chinese medicine usage from the studies on complementary and alternative medicine (CAM). Seventy four (74) out of 81 articles reported rates of CAM usage ranging from 2.6 to 100%. Acupuncture was reported in 71 out of 81 studies. Other less commonly reported modalities included Qigong (n = 17), Chinese herbal medicine (n = 11), Taichi (n = 10), acupressure (n = 6), moxibustion (n = 2), Chinese dietary therapy (n = 1), Chinese massage (n = 1), cupping (n = 1) and other Chinese medicine modalities (n = 19). This review also found important limitations of the English language articles on CAM usage in cancer patients. Our results show that Chinese medicine, in particular Chinese herbal medicine, is commonly used by cancer patients. Further research is warranted to include studies not written in English. 相似文献