全文获取类型
收费全文 | 2822篇 |
免费 | 245篇 |
国内免费 | 168篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 64篇 |
妇产科学 | 14篇 |
基础医学 | 311篇 |
口腔科学 | 200篇 |
临床医学 | 228篇 |
内科学 | 475篇 |
皮肤病学 | 29篇 |
神经病学 | 142篇 |
特种医学 | 56篇 |
外科学 | 116篇 |
综合类 | 478篇 |
现状与发展 | 1篇 |
预防医学 | 143篇 |
眼科学 | 78篇 |
药学 | 732篇 |
中国医学 | 118篇 |
肿瘤学 | 43篇 |
出版年
2023年 | 28篇 |
2022年 | 32篇 |
2021年 | 129篇 |
2020年 | 82篇 |
2019年 | 90篇 |
2018年 | 90篇 |
2017年 | 90篇 |
2016年 | 111篇 |
2015年 | 117篇 |
2014年 | 154篇 |
2013年 | 245篇 |
2012年 | 206篇 |
2011年 | 199篇 |
2010年 | 171篇 |
2009年 | 148篇 |
2008年 | 136篇 |
2007年 | 116篇 |
2006年 | 105篇 |
2005年 | 88篇 |
2004年 | 99篇 |
2003年 | 87篇 |
2002年 | 65篇 |
2001年 | 64篇 |
2000年 | 41篇 |
1999年 | 41篇 |
1998年 | 58篇 |
1997年 | 35篇 |
1996年 | 34篇 |
1995年 | 33篇 |
1994年 | 44篇 |
1993年 | 30篇 |
1992年 | 30篇 |
1991年 | 29篇 |
1990年 | 17篇 |
1989年 | 24篇 |
1988年 | 22篇 |
1987年 | 23篇 |
1986年 | 16篇 |
1985年 | 15篇 |
1984年 | 18篇 |
1983年 | 18篇 |
1982年 | 17篇 |
1981年 | 13篇 |
1980年 | 9篇 |
1979年 | 9篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有3235条查询结果,搜索用时 15 毫秒
11.
Suqin Zhu Mingyong Zeng Wei Guo Guangxin Feng 《journal of environmental science and health part c-environmental carcinogenesis & ecotoxicology reviews》2019,37(2):55-66
Gold nanoparticles (AuNPs) have been previously shown to induce gut dysbiosis during colitis in mice, but the underlying mechanism is not clear yet. Here, we evaluated the effects of AuNPs (5?nm diameter, coated with tannic acid, polyvinylpyrrolidone or citrate) on H2O2 accumulation and pathogen antagonization by an intestinal strain of Lactobacillus gasseri under aerobic cultural conditions. AuNPs (0.65?μg/mL) reduced over 50% of H2O2 accumulation by L. gasseri, and significantly inhibited the antagonistic action of L. gasseri on growth of four foodborne enteric pathogens, i.e. Salmonella enterica serovar Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus in associative cultures. 相似文献
12.
Megumi Ueno Takashi Shimokawa Emiko Sekine-Suzuki Minako Nyui Ikuo Nakanishi Ken-ichiro Matsumoto 《Journal of Clinical Biochemistry and Nutrition》2021,68(2):123
Relatively young (4-week-old) selenium deficient (SeD) mice, which lack the activity of selenium-dependent glutathione peroxidase (GSH-Px) isomers, were prepared using torula yeast-based SeD diet. Mice were fed the torula yeast-based SeD diet and ultra-pure water. Several different timings for starting the SeD diet were assessed. The weekly time course of liver comprehensive GSH-Px activity after weaning was monitored. Protein expression levels of GPx1 and 4 in the liver were measured by Western blot analysis. Gene expression levels of GPx1, 2, 3, 4, and 7 in the liver were measured by quantitative real-time PCR. Apoptotic activity of thymocytes after hydrogen peroxide (H2O2) exposure was compared. Thirty-day survival rates after whole-body X-ray irradiation were estimated. Pre-birth or right-after-birth starting of the SeD diet in dams was unable to lead to creation of SeD mice due to neonatal death. This suggests that Se is necessary for normal birth and healthy growing of mouse pups. Starting the mother on the SeD diet from 2 weeks after giving birth (SeD-trial-2w group) resulted in a usable SeD mouse model. The liver GSH-Px activity of the SeD-trial-2w group was almost none from 4 week olds, but the mice survived for more than 63 weeks. Protein and gene expression of GPx1 was suppressed in the SeD-trial-2w group, but that of GPx4 was not. The thymocytes of the SeD-trial-2w group were sensitive to H2O2-induced apoptosis. The SeD-trial-2w group was sensitive to whole-body X-ray irradiation compared with control mice. The SeD-trial-2w model may be a useful animal model for H2O2/hydroperoxide-induced oxidative stress. 相似文献
13.
Ming Liu Caochuang Wang Pengcheng Li Liang Cheng Yongming Hu Yao Xiong Shishang Guo Haoshuang Gu Wanping Chen 《Materials》2021,14(9)
Many low-dimensional nanostructured metal oxides (MOXs) with impressive room-temperature gas-sensing characteristics have been synthesized, yet transforming them into relatively robust bulk materials has been quite neglected. Pt-decorated SnO2 nanoparticles with 0.25–2.5 wt% Pt were prepared, and highly attractive room-temperature hydrogen-sensing characteristics were observed for them all through pressing them into pellets. Some pressed pellets were further sintered over a wide temperature range of 600–1200 °C. Though the room-temperature hydrogen-sensing characteristics were greatly degraded in many samples after sintering, those samples with 0.25 wt% Pt and sintered at 800 °C exhibited impressive room-temperature hydrogen-sensing characteristics comparable to those of their counterparts of as-pressed pellets. The variation of room-temperature hydrogen-sensing characteristics among the samples was explained by the facts that the connectivity between SnO2 grains increases with increasing sintering temperature, and Pt promotes oxidation of SnO2 at high temperatures. These results clearly demonstrate that some low-dimensional MOX nanocrystals can be successfully transformed into bulk MOXs with improved robustness and comparable room-temperature gas-sensing characteristics. 相似文献
14.
Ronald T. Toth Samantha E. Pace Brittney J. Mills Sangeeta B. Joshi Reza Esfandiary C. Russell Middaugh David D. Weis David B. Volkin 《Journal of pharmaceutical sciences》2018,107(4):1009-1019
Antibodies are molecules that exhibit diverse conformational changes on different timescales, and there is ongoing interest to better understand the relationship between antibody conformational dynamics and storage stability. Physical stability data for an IgG4 monoclonal antibody (mAb-D) were gathered through traditional forced degradation (temperature and stirring stresses) and accelerated stability studies, in the presence of different additives and solution conditions, as measured by differential scanning calorimetry, size exclusion chromatography, and microflow imaging. The results were correlated with hydrogen exchange mass spectrometry (HX-MS) data gathered for mAb-D in the same formulations. Certain parameters of the HX-MS data, including hydrogen exchange in specific peptide segments in the CH2 domain, were found to correlate with stabilization and destabilization of additives on mAb-D during thermal stress. No such correlations between mAb physical stability and HX-MS readouts were observed under agitation stress. These results demonstrate that HX-MS can be set up as a streamlined methodology (using minimal material and focusing on key peptide segments at key time points) to screen excipients for their ability to physically stabilize mAbs. However, useful correlations between HX-MS and either accelerated or real-time stability studies will be dependent on a particular mAb's degradation pathway(s) and the type of stresses used. 相似文献
15.
Sara Matić Milena Jadrijević-Mladar Takač Monika Barbarić Bono Lučić Koraljka Gall Trošelj Višnja Stepanić 《Journal of pharmaceutical sciences》2018,107(11):2957-2964
The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B. 相似文献
16.
Apurva S. More Ronald T. Toth Solomon Z. Okbazghi C. Russell Middaugh Sangeeta B. Joshi Thomas J. Tolbert David B. Volkin David D. Weis 《Journal of pharmaceutical sciences》2018,107(9):2315-2324
We have used hydrogen exchange–mass spectrometry to characterize local backbone flexibility of 4 well-defined IgG1-Fc glycoforms expressed and purified from Pichia pastoris, 2 of which were prepared using subsequent in vitro enzymatic treatments. Progressively decreasing the size of the N-linked N297 oligosaccharide from high mannose (Man8-Man12), to Man5, to GlcNAc, to nonglycosylated N297Q resulted in progressive increases in backbone flexibility. Comparison of these results with recently published physicochemical stability and Fcγ receptor binding data with the same set of glycoproteins provide improved insights into correlations between glycan structure and these pharmaceutical properties. Flexibility significantly increased upon glycan truncation in 2 potential aggregation-prone regions. In addition, a correlation was established between increased local backbone flexibility and increased deamidation at asparagine 315. Interestingly, the opposite trend was observed for oxidation of tryptophan 277 where faster oxidation correlated with decreased local backbone flexibility. Finally, a trend of increasing C'E glycopeptide loop flexibility with decreasing glycan size was observed that correlates with their FcγRIIIa receptor binding properties. These well-defined IgG1-Fc glycoforms serve as a useful model system to identify physicochemical stability and local backbone flexibility data sets potentially discriminating between various IgG glycoforms for potential applicability to future comparability or biosimilarity assessments. 相似文献
17.
Evaluation of a P,N‐ligated iridium(I) catalyst in hydrogen isotope exchange reactions of aryl and heteroaryl compounds 下载免费PDF全文
Mégane Valero Annina Burhop Kristof Jess Remo Weck Matthias Tamm Jens Atzrodt Volker Derdau 《Journal of labelled compounds & radiopharmaceuticals》2018,61(4):380-385
We have developed a novel and efficient iridium‐catalyzed hydrogen isotope exchange reaction method with secondary and tertiary sulfonamides at ambient temperatures. Furthermore N‐oxides and phosphonamides have been successfully applied in hydrogen isotope exchange reactions with moderate to excellent deuterium introduction. 相似文献
18.
19.
目的 研究介孔二氧化硅纳米粒(MSN)载体与装载的难溶性药物间的相互作用,探索对释放速率具有重要影响的因素,归纳总结可预测难溶性药物-MSN给药系统释放行为的数学模型。方法 以溶胶凝胶法制备的MSN作为载体,通过溶剂挥干法进行药物装载,利用扫描电子显微镜(SEM)、透射电子显微镜(TEM)分析载体的外观形貌及孔道结构,通过比表面积分析仪研究载体的比表面积及孔径分布。选取载药量及药物的氢键受体数量作为因素进行释放行为分析,通过Design Expert软件进行2因素3水平析因设计,完成体外释放实验;2、24 h累积释放度作为因变量,拟合数学模型。结果溶胶凝胶法制备的MSN为均一的球形,粒径约为400 nm,孔道呈放射状,孔径均一为3.6 nm。拟合模型显示,载药量比氢键受体数量对2 h累计释放度影响更大,随着载药量的增加,2 h累计释放度逐渐下降;在研究范围内,氢键受体数为6,载药量为50%具有最小的2 h累计释放度,为50.31%。24 h累计释放度则根据载药量的不同随着氢键受体数的改变呈现相反趋势,当载药量较低时,与氢键受体数呈正相关;当载药量较高时,与氢键受体数呈负相关。氢键受体数为6,载药量小于10%时具有最大的24 h累计释放度,可达99.44%。结论 相对药物的氢键受体数量,载药量对于难溶性药物-MSN给药系统的速缓释放具有重要调控作用,低载药量可以实现药物的2 h快速释放及24 h完全释放,高载药量则反之。 相似文献
20.
目的明确氧化应激对视网膜色素上皮细胞(RPE)中去乙酰化酶1(SIRT1)表达的影响。方法以人RPE细胞为实验对象,不同浓度H_2O_2(0、200、300μmol/L)处理RPE细胞,观察处理后24 h细胞形态的改变情况,检测处理后24 h与72 h细胞中SIRT1的mRNA与蛋白表达情况。结果 H_2O_2作用后,随H_2O_2浓度的增加,RPE细胞的形态受损,有凋亡小体的出现;在氧化应激24 h后细胞内SIRT1的转录水平增加,而在氧化应激72 h后SIRT1的蛋白表达显著下降。结论氧化应激可导致RPE细胞形态改变,SIRT1在RPE细胞内维持着氧化与抗氧化应激系统平衡,因此将SIRT1可作为临床上年龄相关性黄斑变性病(AMD)治疗的靶点。 相似文献