全文获取类型
收费全文 | 127429篇 |
免费 | 12378篇 |
国内免费 | 7007篇 |
专业分类
耳鼻咽喉 | 1059篇 |
儿科学 | 1105篇 |
妇产科学 | 1555篇 |
基础医学 | 34113篇 |
口腔科学 | 3846篇 |
临床医学 | 9087篇 |
内科学 | 17125篇 |
皮肤病学 | 2096篇 |
神经病学 | 11257篇 |
特种医学 | 3323篇 |
外国民族医学 | 24篇 |
外科学 | 11835篇 |
综合类 | 17988篇 |
现状与发展 | 25篇 |
一般理论 | 2篇 |
预防医学 | 3601篇 |
眼科学 | 3371篇 |
药学 | 12620篇 |
17篇 | |
中国医学 | 3952篇 |
肿瘤学 | 8813篇 |
出版年
2024年 | 158篇 |
2023年 | 1434篇 |
2022年 | 2132篇 |
2021年 | 3985篇 |
2020年 | 3879篇 |
2019年 | 3432篇 |
2018年 | 3582篇 |
2017年 | 4007篇 |
2016年 | 4454篇 |
2015年 | 5003篇 |
2014年 | 7710篇 |
2013年 | 9503篇 |
2012年 | 7370篇 |
2011年 | 8544篇 |
2010年 | 6983篇 |
2009年 | 6729篇 |
2008年 | 7014篇 |
2007年 | 7058篇 |
2006年 | 6510篇 |
2005年 | 5593篇 |
2004年 | 4853篇 |
2003年 | 4089篇 |
2002年 | 3172篇 |
2001年 | 2717篇 |
2000年 | 2323篇 |
1999年 | 2072篇 |
1998年 | 2028篇 |
1997年 | 1938篇 |
1996年 | 1758篇 |
1995年 | 1728篇 |
1994年 | 1566篇 |
1993年 | 1377篇 |
1992年 | 1190篇 |
1991年 | 1144篇 |
1990年 | 976篇 |
1989年 | 943篇 |
1988年 | 809篇 |
1987年 | 731篇 |
1986年 | 622篇 |
1985年 | 919篇 |
1984年 | 811篇 |
1983年 | 547篇 |
1982年 | 721篇 |
1981年 | 573篇 |
1980年 | 474篇 |
1979年 | 426篇 |
1978年 | 328篇 |
1977年 | 257篇 |
1976年 | 246篇 |
1975年 | 99篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
Lamberto Torralba‐Raga Bianca Tesi Samuel C. C. Chiang Heinrich Schlums Magnus Nordenskjld AnnaCarin Horne Jan‐Inge Henter Marie Meeths Mohamed Abdelhaleem Sheila Weitzman Yenan Bryceson 《Pediatric blood & cancer》2020,67(4)
Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21‐year‐old patient with fatal Epstein‐Barr virus infection–associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by >95%. Three healthy brothers carried the SH2D1A c.49G > A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. Importantly, our results highlight challenges in the clinical interpretation of SH2D1A variants and caution in using functional flow cytometry assays for the diagnosis of XLP1. 相似文献
62.
目的:探索原肌球蛋白4(Tropomyosin4,TPM4)在胃癌细胞的迁移、侵袭和转移中的作用。方法:利用Real-time PCR、Western Blot及免疫荧光,检测原肌球蛋白4在不同胃癌细胞系及正常胃上皮细胞中的表达情况;利用免疫组化,检测原肌球蛋白4在胃癌组织及癌旁正常组织中的表达情况;利用慢病毒技术,在GC9811-P细胞中,分别转染LV-TPM4、shRNA-TPM4及对照空载体;通过Transwell和体内实验,检测胃癌细胞迁移、侵袭和转移。结果:Real-time PCR、Western Blot及免疫组化结果显示,原肌球蛋白4在胃癌细胞系及胃癌组织中的表达降低;上调原肌球蛋白4的表达后,抑制胃癌细胞的迁移、侵袭和转移;下调原肌球蛋白4的表达后,促进胃癌细胞的迁移、侵袭和转移(P<0.05)。结论:原肌球蛋白4抑制胃癌细胞的迁移、侵袭和转移。 相似文献
63.
64.
65.
Sheng Zhang Yan Wang Jie Xu Bokyung Kim Wenbin Deng Fuzheng Guo 《The Journal of neuroscience》2021,41(2):251
The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury. 相似文献
66.
《Vaccine》2020,38(33):5337-5342
Freezing of alum-based vaccines drastically alters their colloidal composition and leads to irreversible cluster formation. The loss of stability is well described, but the impact of frost damage on the functionality of the induced and secreted antibody repertoire has not been studied in detail. We therefore applied our single-cell measurement platform to extract the frequencies of Immunoglobulin G-secreting cells in combination with individual secretion rates and affinities. We showed that, frost-damaged or not, the tested vaccine was able to generate similar frequencies of total and antigen-affine IgG-secreting cells. Additionally, the frost-damaged vaccine stimulated a similar T-cell cytokine secretion pattern when compared to the regularly stored vaccine. However, frost-damaged vaccines induced no efficient affinity maturation and a complete collapse of the affinity distribution was observed. This study unveiled the impact of frost-damage to alum-based vaccines on the induced secreted antibody repertoire, and illustrated the power of functional single-antibody analysis. 相似文献
67.
Yong Luo Yang Zou Li-ping Li Zhao-zhen Wang Li-qun Wang Zi-yu Zhang 《Gynecological endocrinology》2020,36(10):895-901
AbstractOxidative stress (OS) has been proposed to play a role in the development of EMs. Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. The Western blotting results showed that the relative expression of PRDX4 was significantly increased in ectopic endometria compared with the normal endometria of EMs-free (p?<?.05). The H2O2 concentration was also significantly higher in the ectopic endometrium. PRDX4 siRNA was transfected into primary ectopic endometrial stromal cells (EESCs). The viability of the transfected EESCs was measured by CCK-8 assay, and the results showed significantly decreased cell viability. Furthermore, the apoptosis rate and ROS generation in flow cytometry assays were significantly increased after the knockdown of PRDX4 expression (p?<?.05). Scratch assays and transwell assays revealed that decreased expression of PRDX4 mediated by siRNA inhibited EESC migration and invasion. In conclusion, these findings indicate the potential role of PRDX4 in the development of EMs and PRDX4 as a possible therapeutic target for EMs treatment. 相似文献
68.
《Biomaterials》2015
Significant efforts have been invested into the differentiation of stem cells into functional hepatocyte-like cells that can be used for cell therapy, disease modeling and drug screening. Most of these efforts have been concentrated on the use of growth factors to recapitulate developmental signals under in vitro conditions. Using small molecules instead of growth factors would provide an attractive alternative since small molecules are cell-permeable and cheaper than growth factors. We have developed a protocol for the differentiation of human embryonic stem cells into hepatocyte-like cells using a predominantly small molecule–based approach (SM-Hep). This 3 step differentiation strategy involves the use of optimized concentrations of LY294002 and bromo-indirubin-3’-oxime (BIO) for the generation of definitive endoderm; sodium butyrate and dimethyl sulfoxide (DMSO) for the generation of hepatoblasts and SB431542 for differentiation into hepatocyte-like cells. Activin A is the only growth factor required in this protocol. Our results showed that SM-Hep were morphologically and functionally similar or better compared to the hepatocytes derived from the growth-factor induced differentiation (GF-Hep) in terms of expression of hepatic markers, urea and albumin production and cytochrome P450 (CYP1A2 and CYP3A4) activities. Cell viability assays following treatment with paradigm hepatotoxicants Acetaminophen, Chlorpromazine, Diclofenac, Digoxin, Quinidine and Troglitazone showed that their sensitivity to these drugs was similar to human primary hepatocytes (PHHs). Using SM-Hep would result in 67% and 81% cost reduction compared to GF-Hep and PHHs respectively. Therefore, SM-Hep can serve as a robust and cost effective replacement for PHHs for drug screening and development. 相似文献
69.