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141.
Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo. 总被引:2,自引:0,他引:2
Niclas Petri Christer Tannergren Birgit Holst Fred A Mellon Yongping Bao Geoff W Plumb Jim Bacon Karen A O'Leary Paul A Kroon Lars Knutson Patrik Forsell Thomas Eriksson Hans Lennernas Gary Williamson 《Drug metabolism and disposition》2003,31(6):805-813
For the first time the human intestinal effective permeability, estimated from the luminal disappearance and intestinal metabolism of phytochemicals, sulforaphane and quercetin-3,4'-glucoside, as well as the simultaneous changes in gene expression in vivo in enterocytes, has been studied in the human jejunum in vivo (Loc-I-Gut). Both compounds as components of an onion and broccoli extract could readily permeate the enterocytes in the perfused jejunal segment. At the physiologically relevant, dietary concentration tested, the average effective jejunal permeability (Peff) and percentage absorbed (+/- S.D.) were 18.7 +/- 12.6 x 10-4 cm/s and 74 +/- 29% for sulforaphane and 8.9 +/- 7.1 x 10-4 cm/s and 60 +/- 31% for quercetin-3,4'-diglucoside, respectively. Furthermore, a proportion of each compound was conjugated and excreted back into the lumen as sulforaphane-glutathione and quercetin-3'-glucuronide. The capacity of the isolated segment to deconjugate quercetin from quercetin-3,4'-diglucoside during the perfusion was much higher than the beta-glucosidase activity of the preperfusion jejunal contents, indicating that the majority (79-100%) of the beta-glucosidase capacity derives from the enterocytes in situ. Simultaneously, we determined short-term changes in gene expression in exfoliated enterocytes, which showed 2.0 +/- 0.4-fold induction of glutathione transferase A1 (GSTA1) mRNA (p < 0.002) and 2.4 +/- 1.2-fold induction of UDP-glucuronosyl transferase 1A1 (UGT1A1) mRNA (p < 0.02). The changes in gene expression were also seen in differentiated Caco-2 cells, where sulforaphane was responsible for induction of GSTA1 and quercetin for induction of UGT1A1. These results show that food components have the potential to modify drug metabolism in the human enterocyte in vivo very rapidly. 相似文献
142.
143.
红细胞不仅可以运送氧、二氧化碳和清除循环免疫复合物,还能够识别、黏附、提呈肿瘤抗原,此外红细胞能够促进免疫细胞吞噬和杀伤肿瘤细胞的能力,因此红细胞在机体抗肿瘤免疫发挥重要作用。近年来,红细胞也可以开发作为药物载体治疗肿瘤,这与红细胞自身具有生物相容性和半透膜的特性有关。药物可以倍助渗透压梯度的不同、抗生素提高膜通透性,膜受体介导连接,以及交联介导连接等方法载入。已载入红细胞的药物半衰期延长,缓慢释放,受体液中酶等具有生物活性的物质降解,并且可以减轻药物毒副作用。缺点在于其靶向性单一。 相似文献
144.
Objective To develop a method for absolute quantification of interleukin 8 (IL—8) mRNA by using real-time polymerase chain reaction
(PCR).
Methods The IL —8 mRNA and protein expression in 2 human lung cancer cell lines, H460 and A549, were evaluated by real-time PCR and
ELISA. The IL-8 mRNA expression in 9 cases of normal lung tissue and 44 cases of non-small cell lung cancer (NSCLC) were examined.
Results The IL—8 mRNA copy number in a given sample can be measured by real-time PCR. The gene expression of IL—8 is correlated with
its protein secretion. The normalized value of IL—8 expression was 4.87±1.69 (copies/ 104 GAPDH copies) in normal lung tissue and 17.04 ±23.96 in NSCLC, respectively. The difference between these two groups is statistically
significant (P=0.002). Using 9.74 and 19.48 as cut-off points for positive expression and overexpression of IL—8, 52.3%(23/44cases) of NSCLC
were found to express an increased level of IL-8, among which 29.5% (13/ 44cases) were defined as positive expression and
22.7%(10/44cases) as overexpression. Statistical analysis indicated that IL—8 overexpression was significantly increased in
female cancers, squamous carcinoma, and in late stages of disease (P<0.05).
Conclusion The IL—8 gene expression can be determined by a real-time PCR technique. IL -8 overexpression is correlated with gender, histopathology
and stages of the disease. 相似文献
145.
146.
Blast exposure causes redistribution of phosphorylated neurofilament subunits in neurons of the adult rat brain 总被引:5,自引:0,他引:5
There is little information on threshold levels and critical time factors for blast exposures, although brain damage after a blast has been established both clinically and experimentally. Moreover, the cellular pathophysiology of the brain response is poorly characterized. This study employs a rat model for blast exposure to investigate effects on the neuronal cytoskeleton. Exposure in the range of 154 kPa/198 dB or 240 kPa/202 dB has previously been shown neither to cause visual damage to the brain, nor to affect the neuronal populations, as revealed with routine histology. Here, the brains were investigated immunohistochemically from 2 h to 21 days after blast exposure. A monoclonal antibody was used which detects only the phosphorylated epitope of the heavy subunit of the neurofilament proteins (p-NFH). This epitope is normally restricted to axons, that is, not demonstrable in the perikarya. Eighteen hours after exposure in the 240-kPa/202-dB range, p-NFH immunoreactivity accumulated in neuronal perikarya in layers II-IV of the temporal cortex and of the cingulate and the piriform cortices, the dentate gyrus and the CA1 region of the hippocampus. At the same time, the p-NFH immunoreactivity disappeared from the axons and dendrites of cerebral cortex neurons. The most pronounced immunostaining of neuronal perikarya was found in the hemisphere, which faced the blast source. The perikaryal accumulation of p-NFH was present also at 7 days but the neuronal perikarya had become negative at 21 days, at which time the axons again displayed p-NFH immunoreactivity. Exposure in the range of 154 kPa/198 dB caused similar, although less marked accumulation of p-NFH immunoreactivity in the neuronal perikarya. The findings are interpreted to show a dephosphorylation of NFHs in axons and dendrites and a piling up of p-NFHs in the perikarya due to disturbed axonal transport. 相似文献
147.
目的 了解十二指肠胃食管反流(DGER)所致急性气管炎的病理学变化。方法 将实验组的幼兔复制成DGER动物模型,应用光镜和扫描电镜观察气管组织。结果 气管粘膜层的纤毛及柱状上皮细胞变性、脱落;粘膜下层炎性水肿。结论 DGER反流液中的胃酸和胆汁酸等双重攻击因子可直接导致气管的化学性炎症损伤。 相似文献
148.
医疗法学在医务人员再教育中的地位 总被引:51,自引:0,他引:51
随着社会的文明进步,特别是在法制越来越健全的社会,作为医务人员在培养业务技能的同时,接受医疗法学再教育有着非常重要的意义。文章论述了医疗法学的概念及其存在、发展的客观事实;医疗法学在医疗实践中的作用;医疗法学在医务人员继续教育体系中的地位和意义。 相似文献
149.
用pH值敏感荧光探针Snaflcalcein-AM标记体外培养48小时的小鼠腹腔巨噬细胞,570型粘附式细胞仪观察巨噬细胞在对刀豆素A进行受体介导内吞过程中细胞内pH值的变化。结果显示,开始内吞后细胞内pH值即降低,内吞进行到第5分钟细胞内pH值降到最低,在此后的6分钟内均维持于这一较低水平。本法灵敏度高,简便快捷,适用范围广,可无损伤观察活细胞或细胞器pH值的变化。 相似文献
150.
人肿瘤裸鼠移植瘤株模型转移抑制基因nm23-H1mRNA的表达 总被引:1,自引:0,他引:1
目的nm23基因与肿瘤移植瘤株转移的关系。方法应用地高辛标记的nm23┐H1反义cRNA探针原位杂交方法对人克隆化肝癌,人骨肉瘤,肾癌三种不同肿瘤的裸鼠移植瘤株模型(H┐CS,M┐OS,M┐RCC)中瘤内nm23┐H1进行检测。结果nm23H1mRNA在三模型中均有不同程度快的表达,其中有较强转移能力的H┐CS,和潜伏期短、侵袭生长速度快的M┐RCC杂交信号50%为弱阳性,而M┐OS仅有25%为弱阳性。结论nm23的弱阳性表达可能和H┐CS生长速度及转移倾向有一定联系。 相似文献