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91.
Lingo‐1 Inhibited by RNA Interference Promotes Functional Recovery of Experimental Autoimmune Encephalomyelitis 下载免费PDF全文
Chun‐Juan Wang Chuan‐Qiang Qu Jie Zhang Pei‐Cai Fu Shou‐Gang Guo Rong‐Hua Tang 《Anatomical record (Hoboken, N.J. : 2007)》2014,297(12):2356-2363
Lingo‐1 is a negative regulator of myelination. Repairment of demyelinating diseases, such as multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), requires activation of the myelination program. In this study, we observed the effect of RNA interference on Lingo‐1 expression, and the impact of Lingo‐1 suppression on functional recovery and myelination/remyelination in EAE mice. Lentiviral vectors encoding Lingo‐1 short hairpin RNA (LV/Lingo‐1‐shRNA) were constructed to inhibit Lingo‐1 expression. LV/Lingo‐1‐shRNA of different titers were transferred into myelin oligodendrocyte glycoprotein‐induced EAE mice by intracerebroventricular (ICV) injection. Meanwhile, lentiviral vectors carrying nonsense gene sequence (LVCON053) were used as negative control. The Lingo‐1 expression was detected and locomotor function was evaluated at different time points (on days 1,3,7,14,21, and 30 after ICV injection). Myelination was investigated by luxol fast blue (LFB) staining.LV/Lingo‐1‐shRNA administration via ICV injection could efficiently down‐regulate the Lingo‐1 mRNA and protein expression in EAE mice on days 7,14,21, and 30 (P < 0.01), especially in the 5 × 108 TU/mL and 5 × 109 TU/mL LV/Lingo‐1‐shRNA groups. The locomotor function score in the LV/Lingo‐1‐shRNA treated groups were significantly lower than the untreated or LVCON053 group from day 7 on. The 5 × 108 TU/mL LV/Lingo‐1‐shRNA group achieved the best functional improvement (0.87 ± 0.11 vs. 3.05 ± 0.13, P < 0.001). Enhanced myelination/remyelination was observed in the 5 × 107, 5 × 108, 5 × 109 TU/mL LV/Lingo‐1‐shRNA groups by LFB staining (P < 0.05, P < 0.01, and P < 0.05).The data showed that administering LV/Lingo‐1‐shRNA by ICV injection could efficiently knockdown Lingo‐1 expression in vivo, improve functional recovery and enhance myelination/remyelination. Antagonism of Lingo‐1 by RNA interference is, therefore, a promising approach for the treatment of demyelinating diseases, such as MS/EAE. Anat Rec, 297:2356–2363, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
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Both dopamine D1 and D2 receptors are present in rat retina. D1 receptors are positively coupled to adenylyl cyclase, while D2 receptors are negatively coupled. After intraocular administration of the neurotoxin 6-hydroxydopamine (6-OHDA) there is depletion of retinal dopamine by about 90%, as well as a decrease of the number of D1 and D2 receptor binding sites. Following the 6-OHDA lesion, there is an enhancement of the D1 receptor-stimulated accumulation of cyclic-AMP and a loss of D2 receptor-inhibited accumulation of cyclic-AMP. Our results suggest that some of the retinal D2 receptors are coupled to adenylyl cyclase and some are not. 相似文献
95.
Jane J. Y. Liu Cheng-Long Bai Ann M. Williamson Shu-Xin Qu Hanan Hamdan Neill H. Stacey 《International archives of occupational and environmental health》1996,69(1):21-26
The effects of exposure to solvents on serum bile acids were investigated by comparing a group of apprentice vehicle spray
painters (exposed group) with one of apprentice electricians. Apprentice spray painters from the study were subdivided into
high-and low-solvent-exposure groups. Concentrations of individual serum bile acids (SBA) were measured and compared with
conventional liver function tests (LFTs). Total, free, glycine-and taurine-conjugated SBA were consistently found to be present
at higher levels in the spray painters than in the electricians, even at the beginning of the apprenticeship. Total SBA tended
to increase in spray painters with increasing years of exposure during the apprenticeship, but this was significant at only
one time point. No rises were observed over the sampling period in electricians. The mean values of individual and total SBA
concentrations were all found to be higher in the high-exposure group than in the low-exposure group, with some differences
reaching statistical significane. None of the routine liver biochemistry parameters was different between spray painters and
electricians. γ-Glutamyl transferase (GGT) was the only enzyme found to be significantly different between the high-and low-exposure
groups, but all values were within the normal range. This study suggests that occupational exposure even to low levels of
solvent mixtures results in increases in SBA. The increased SBA may be indicative of a subclinical liver dysfunction. Alternatively,
they may reflect solvent exposure only, with the raised levels having no pathologic implication or consequence.
The views expressed in this article are those of the authors and do not necessarily reflect those of the National Occupational
Health and Safety Commission 相似文献
96.
复方夜灵胶囊中大黄素的含量测定 总被引:3,自引:0,他引:3
目的:建立复方夜灵胶囊中大黄素的含量测定方法。方法:采用酸水解和氯仿回流提取的方法制备供试液,HPLC法测定复方夜灵胶囊中大黄素的含量,色谱条件为流动相:甲醇-0.2 mol·L~(-1)磷酸二氢钠溶液(80:20,磷酸调节至 pH=3.0),检测波长444nm,流速为1.0 ml·min~(-1)。结果:大黄素的回归方程为 A=-5181.36 55503.53 C,(r=0.999 6),线性范围为0.046~0.152μg,本法的平均回收率为98.25%,RSD 为2.66%。结论:采用本法测定复方夜灵胶囊中大黄素含量操作简便,结果准确、可靠,可作为本品的质量控制标准之一。 相似文献
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Zhang SS Zhang HQ Li D Sun LH Ma CP Wang W Wan J Qu B 《European journal of pharmacology》2008,584(1):144-152
Benzotriazole derivatives have been shown to be able to induce growth inhibition in cancer cells. In the present study, we synthesized bioactive compound, 3-(1H-benzo [d] [1,2,3] triazol-1-yl)-1-(4-methoxyphenyl)-1-oxopropan-2-yl benzoate (BmOB), which is a novel benzotriazole derivative. BmOB displayed anti-proliferative effects on several human tumor cell lines. Human hepatocarcinoma BEL-7402 cell line was selected as a model to illustrate BmOB's inhibition effect and its potential mechanism, since it was the highest susceptible cell line to BmOB. It was shown that treatment with BmOB resulted in generation of reactive oxygen species, disruption of mitochondrial membrane potential (DeltaPsim), and cell death in BEL-7402 cells. BmOB induced cytotoxicity could be prevented by antioxidant vitamin C and mitochondrial permeability transition inhibitor cyclosporine A. cyclosporine A could also protect the BmOB induced collapse of DeltaPsim in BEL7402 cells, while vitamin C did not show similar effects. The results suggest that BmOB could inhibit BEL-7402 cell proliferation, and the cell death may occur through the modulation of mitochondrial functions regulated by reactive oxygen species. It appears that collapse of DeltaPsim prior to intracellular reactive oxygen species arose during the cytotoxic process in our experimental system. 相似文献
99.
血清CEA、NSE、Cyfra21-1水平与肺癌分期、近期疗效及生存时间的相关性研究 总被引:3,自引:0,他引:3
目的研究肺癌患者血清CEA、NSE、Cyfra21-1水平与肺癌分期、近期疗效及生存时间的关系.方法确诊为肺癌的患者,化疗前、后常规检查血清CEA、NSE、Cyfra21-1,评估其变化,所有入组患者随访5年.结果96例肺癌患者中,血清肿瘤标志物增高者为66.67%(64/96),其中SCLC为64.71%(22/34);NSCLC为67.74%(42/62);SCLC患者血清CEA、NSE、Cy-fra21-1增高的发生率分别为8.82%(3/34)、55.88%(19/34)及29.41%(10/34);NSCLC患者分别为35.48%(22/62)、19.35%(12/62)及43.65%(27/62);其中肺腺癌分别为45.24%(19/42)、11.90%(5/42)及38.10%(16/42),肺鳞癌分别为18.75%(3/16)、31.25%(5/16)及56.25%(9/16);SCLC局限期分别为0%、15.79%(3/19)及0%,广泛期分别为100%(3/3)、84.21%(16/19)及100%(10/10);ⅢB期NSCLC分别为9.09%(2/22)、0%及11.11%(3/27);Ⅳ期分别为90.91%(20/22)、100%(14/14)及88.89%(24/27);化疗后,SCLC血清NSE降至正常者为94.74%(18/19),NSCLC血清CEA、Cyfra21-1降低或降至正常者分别为68.18%(15/22)及92.6%(25/27);SCLC血清肿瘤标志物增高的总生存期为18.18个月;NSCLC为16.36个月.结论血清肿瘤指标与肺癌分期、疗效及生存时间有关,晚期肿瘤标志物增高,化疗后明显下降,增高的患者预后差、生存时间短. 相似文献
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