全文获取类型
收费全文 | 44998篇 |
免费 | 4519篇 |
国内免费 | 3602篇 |
专业分类
耳鼻咽喉 | 401篇 |
儿科学 | 478篇 |
妇产科学 | 624篇 |
基础医学 | 5435篇 |
口腔科学 | 998篇 |
临床医学 | 5903篇 |
内科学 | 6665篇 |
皮肤病学 | 515篇 |
神经病学 | 2374篇 |
特种医学 | 1717篇 |
外国民族医学 | 20篇 |
外科学 | 4650篇 |
综合类 | 7760篇 |
现状与发展 | 15篇 |
一般理论 | 6篇 |
预防医学 | 3014篇 |
眼科学 | 1204篇 |
药学 | 4635篇 |
28篇 | |
中国医学 | 2815篇 |
肿瘤学 | 3862篇 |
出版年
2024年 | 117篇 |
2023年 | 627篇 |
2022年 | 1595篇 |
2021年 | 2264篇 |
2020年 | 1725篇 |
2019年 | 1460篇 |
2018年 | 1596篇 |
2017年 | 1474篇 |
2016年 | 1351篇 |
2015年 | 2012篇 |
2014年 | 2554篇 |
2013年 | 2193篇 |
2012年 | 3201篇 |
2011年 | 3499篇 |
2010年 | 2115篇 |
2009年 | 1750篇 |
2008年 | 2241篇 |
2007年 | 2313篇 |
2006年 | 2277篇 |
2005年 | 2071篇 |
2004年 | 1701篇 |
2003年 | 1821篇 |
2002年 | 1633篇 |
2001年 | 1395篇 |
2000年 | 1226篇 |
1999年 | 1316篇 |
1998年 | 876篇 |
1997年 | 806篇 |
1996年 | 637篇 |
1995年 | 587篇 |
1994年 | 512篇 |
1993年 | 259篇 |
1992年 | 348篇 |
1991年 | 289篇 |
1990年 | 271篇 |
1989年 | 220篇 |
1988年 | 212篇 |
1987年 | 172篇 |
1986年 | 144篇 |
1985年 | 91篇 |
1984年 | 76篇 |
1983年 | 33篇 |
1982年 | 18篇 |
1981年 | 15篇 |
1980年 | 14篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
901.
Feng Zhu Chu Qin Lin Tao Xin Liu Zhe Shi Xiaohua Ma Jia Jia Ying Tan Cheng Cui Jinshun Lin Chunyan Tan Yuyang Jiang Yuzong Chen 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(31):12943-12948
Many drugs are nature derived. Low drug productivity has renewed interest in natural products as drug-discovery sources. Nature-derived drugs are composed of dozens of molecular scaffolds generated by specific secondary-metabolite gene clusters in selected species. It can be hypothesized that drug-like structures probably are distributed in selective groups of species. We compared the species origins of 939 approved and 369 clinical-trial drugs with those of 119 preclinical drugs and 19,721 bioactive natural products. In contrast to the scattered distribution of bioactive natural products, these drugs are clustered into 144 of the 6,763 known species families in nature, with 80% of the approved drugs and 67% of the clinical-trial drugs concentrated in 17 and 30 drug-prolific families, respectively. Four lines of evidence from historical drug data, 13,548 marine natural products, 767 medicinal plants, and 19,721 bioactive natural products suggest that drugs are derived mostly from preexisting drug-productive families. Drug-productive clusters expand slowly by conventional technologies. The lack of drugs outside drug-productive families is not necessarily the result of under-exploration or late exploration by conventional technologies. New technologies that explore cryptic gene clusters, pathways, interspecies crosstalk, and high-throughput fermentation enable the discovery of novel natural products. The potential impact of these technologies on drug productivity and on the distribution patterns of drug-productive families is yet to be revealed. 相似文献
902.
903.
904.
Jieqing Zhu Longfei Chen Juan Shi Shilian Liu Yanxin Liu Dexian Zheng 《Immunology》2014,141(2):211-221
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor (TRAIL-R) play important roles in immune regulation and cancer cell death. Although TRAIL has been shown to induce chemokine release in various tumour cells, the function of TRAIL-R in the development of colitis and colitis-associated carcinogenesis has not been explored. In this study, we found that TRAIL-R-deficient mice exhibited a higher incidence of colitis and colitis-associated cancer than that of wild-type (WT) mice, and TRAIL-R expression was down-regulated in WT mice that were fed dextran sulphate sodium. Chemokines, including CCL2 and CXCL1, were highly expressed in the serum and inflammatory colon tissues of TRAIL-R−/− mice compared with WT mice, and TRAIL-R−/− mice showed a marked infiltration of immune cells during colitis. Hyperactivation of Janus kinase and nuclear factor-κB in colon epithelial cells was also observed, which correlated with the severity of colonic inflammation in TRAIL-R−/− mice. These data suggest that TRAIL-R plays a protective role in chemical-induced colon injury and negatively regulates mucosal immune responses. 相似文献
905.
Ling-Dan Li Wen-Chao Li Cheng-Wu Liu Wei-Jing Shi Peng-Tao Gong Jian-Hua Li Guo-Cai Zhang Ju Yang He Li Xi-Chen Zhang 《Parasitology research》2012,111(5):1929-1935
Pulsatilla chinensis is a medicinal root plant that has been used to treat a wide range of disease conditions. Our study determined the antiprotozoal activity of various P. chinensis extracts and fractions against Giardia intestinalis including their effects on parasite growth, cell viability, adherence, and morphology. Ethyl acetate extracts (IC50?=?257.081?μg/ml) were the most active to inhibit the growth of G. intestinalis followed by aqueous extract (PWE), saponins, and n-butanol extract. The PWE and ethyl acetate extract inhibited G. intestinalis trophozoites adherence after 3?h of incubation and killed almost 50?% of the parasite population in a time-dependent manner. Changes in morphology, presence of precipitates in the cytoplasm, dissolved cytoplasm with large vacuole, break of flagella and ventral disk, membrane blebs, and intracellular and nuclear clearance of the treated trophozoites were observed by scanning and transmission electron microscopy. We demonstrated that P. chinensis induced these changes in G. intestinalis morphology and consequently has potential therapeutic use against giardiasis. 相似文献
906.
Xin Li Lanling Jia Xinshan Jia Mumu Shi Xiaolei Li Xulv Ye Ruiyue Wang Yanlei Xiong Enhua Wang Fang Li 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2013,121(7):612-625
Most adult stem cells are in the G0 phase of the cell cycle, accounting for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. The anti‐tumor drug 5‐fluorouracil (5‐FU) selectively kills proliferating cells, sparing cells in the G0 phase. Thus, the objective of this study was to determine whether 5‐FU can be used to enrich stem cells in a human bronchial epithelial (HBE) cell population in vitro. Side population (SP) cells were isolated from untreated HBE cells or HBE cells treated with 5‐FU, and the resulting cells were subjected to colony formation assays, culturing of cell spheres, and tumorigenicity assays. Expression of Oct3/4, Sox2, PCK, and β‐catenin were examined by Western blot analysis and immunofluorescence. Treatment with 5‐FU increased the percentage of SP cells from 0.3% to 1.5%, and the clonogenic ability of 5‐FU‐treated cells was more than twofold higher than that of HBE cells. Cells that survived after 5‐FU treatment exhibited a higher capacity for sphere formation. Furthermore, spheres formed from 5‐FU‐treated cells possessed the capacity to generate differentiated progenies. Cells treated with 5‐FU also exhibited tumorigenic potential, based on tumor formation assays in nude mice, and Oct3/4‐positive cell aggregates were identified in the resulting tumors. In this study, we have shown that 5‐FU treatment enriched the population of cells expressing the putative embryonic markers Oct3/4 and Sox2 and exhibiting nuclear accumulation of β‐catenin. Furthermore, 5‐FU‐treated cells expressed low levels of the epithelial differentiation marker PCK. Analysis of epigenetic modifications suggested that Oct3/4‐positive cells possessed characteristics of stem cells. These results demonstrate that treatment with 5‐FU can enrich the stem cell population present in a human bronchial epithelial cell line, and implicate combined treatment with 5‐FU and serum‐free medium as a new method for isolation of stem‐like cells from the HBE cell line. 相似文献
907.
908.
909.
910.
The purpose of present study was to investigate the impact of butyl benzyl phthalate (BBP) on SH‐SY5Y neuroblastoma cells in vitro. The cell counting kit‐8 was used to measure cell proliferation and flow cytometry was utilized to study cell cycle phases and apoptosis. Western blotting and quantitative real‐time polymerase chain reaction were used to detect levels of aromatase, estrogen receptors (ERs) and some apoptosis and cell cycle‐related genes. Results showed BBP‐stimulated SH‐SY5Y cells in a dose‐dependent manner and produced a reverted U‐shaped dose‐response curve. BBP at lower concentrations (0.01 and 0.1 μm ) significantly induced cell proliferation while inhibited cell growth at 300 μm . The promoting effect of estradiol could be entirely blocked by administration of ICI182 780, a pure antagonist of ERs, while the effect of BBP could be partly blocked. Additionally, we confirmed 0.1 μm BBP‐induced cell proliferation caused the arrest of cells in S phase and inhibited apoptosis, which might be partially explained by the decreased expression of p53, the increased expression of proliferating cell nuclear antigen, Bcl‐2 and cell cycle regulator cyclin‐D1, and the activation of aromatase. The addition of ICI182 780 had no effect on BBP‐induced ERβ mRNA expression, whereas ICI182 780 could effectively counteract the effect of estradiol. Moreover, pretreatment with ICI182 780 could block the induction of aromatase protein expression and activity by BBP, showing an involvement of ERs. Except for the ER pathway, these results showed there might be other pathways involved in promoting the effects of low‐level BBP on SH‐SY5Y cells, which require further investigation. 相似文献