全文获取类型
收费全文 | 52792篇 |
免费 | 4278篇 |
国内免费 | 2365篇 |
专业分类
耳鼻咽喉 | 326篇 |
儿科学 | 818篇 |
妇产科学 | 1284篇 |
基础医学 | 11905篇 |
口腔科学 | 935篇 |
临床医学 | 3829篇 |
内科学 | 8467篇 |
皮肤病学 | 775篇 |
神经病学 | 2494篇 |
特种医学 | 1674篇 |
外国民族医学 | 9篇 |
外科学 | 2533篇 |
综合类 | 7532篇 |
现状与发展 | 11篇 |
预防医学 | 3632篇 |
眼科学 | 503篇 |
药学 | 5057篇 |
4篇 | |
中国医学 | 957篇 |
肿瘤学 | 6690篇 |
出版年
2024年 | 18篇 |
2023年 | 523篇 |
2022年 | 734篇 |
2021年 | 1335篇 |
2020年 | 1384篇 |
2019年 | 1331篇 |
2018年 | 1341篇 |
2017年 | 1561篇 |
2016年 | 1789篇 |
2015年 | 2119篇 |
2014年 | 2923篇 |
2013年 | 3704篇 |
2012年 | 2905篇 |
2011年 | 3381篇 |
2010年 | 2827篇 |
2009年 | 2884篇 |
2008年 | 2981篇 |
2007年 | 3016篇 |
2006年 | 2951篇 |
2005年 | 2585篇 |
2004年 | 2391篇 |
2003年 | 2001篇 |
2002年 | 1722篇 |
2001年 | 1561篇 |
2000年 | 1281篇 |
1999年 | 1012篇 |
1998年 | 839篇 |
1997年 | 734篇 |
1996年 | 640篇 |
1995年 | 700篇 |
1994年 | 692篇 |
1993年 | 470篇 |
1992年 | 486篇 |
1991年 | 393篇 |
1990年 | 346篇 |
1989年 | 295篇 |
1988年 | 248篇 |
1987年 | 159篇 |
1986年 | 177篇 |
1985年 | 219篇 |
1984年 | 173篇 |
1983年 | 69篇 |
1982年 | 93篇 |
1981年 | 97篇 |
1980年 | 93篇 |
1979年 | 76篇 |
1978年 | 61篇 |
1977年 | 34篇 |
1976年 | 40篇 |
1975年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
51.
Nathan Scudder James Robertson Sally F. Kelty Simon J. Walsh Dennis McNevin 《The Australian journal of forensic sciences》2020,52(2):235-241
ABSTRACTForensic DNA analysis is dependent on comparing the known and the unknown. Expand the number of known profiles, and the likelihood of a successful match increases. Forensic use of DNA is moving towards comparing samples of unknown origin with publicly available genetic data, such as the records held by genetic genealogy providers. Use of forensic genetic genealogy has yielded a number of recent high-profile successes but has raised ethical and privacy concerns. Navigating family trees is complex, even more so when combined with a comparison of genetic relationships. This intelligence-gathering process has led to occasional false leads, and its use also risks a public backlash, similar to concerns over Cambridge Analytica. A cautious approach to use of this technique is therefore warranted. 相似文献
52.
The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells
Cheng Wang Hongyang Li Pengcheng Ma Jianfang Sun Lingjun Li Jun Wei Lei Tao Kun Qian 《Fundamental & clinical pharmacology》2020,34(3):380-388
Epidermal proliferative diseases consisted of a series of common skin diseases, most of which were recurrent chronic skin diseases, and had greatly negative influence on the life quality of patient. Retinoids exhibited vital roles in the treatment of many skin diseases. Our recent study demonstrated that adapalene significantly inhibited the growth of HaCat cells, and the inhibitory activity was stronger than other retinoids, such as all-trans-retinoic acid, acitretin, isotretinoin, tazarotene, and bexarotene. Further study showed that adapalene suppressed the colony formation of HaCat cells, and it dramatically triggered S-phase arrest and apoptosis, rather than G1 phase arrest which was reported in other retinoids in several studies. Additionally, adapalene treatment greatly upregulated the protein expression of DNA damage marker γ-H2AX, which was in accord with the results of the elongation of tail moment by comet electrophoresis analysis. Moreover, DNA damage was triggered and DNA repair was suppressed synchronously with adapalene treatment, which accounted for the mechanism of S-phase arrest induced by adapalene. In summary, our recent work demonstrated that adapalene showed strong anti-proliferation activity in HaCat cells and could be an alternative agent for the epidermal proliferative disease. 相似文献
53.
Mohamed E. Salem J. Nicholas Bodor Alberto Puccini Joanne Xiu Richard M. Goldberg Axel Grothey W. Michael Korn Anthony F. Shields William M Worrilow Edward S. Kim Heinz-Josef Lenz John L. Marshall Michael J. Hall 《International journal of cancer. Journal international du cancer》2020,147(10):2948-2956
Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI. 相似文献
54.
Amir FarmohammadiAli MomeniBanafshe BahmaniHossein GhorbaniRamin Ramzanpour 《Asian Pacific journal of cancer prevention》2020,21(1):255-258
Background: Paraoxonase 1 (PON1), a multifactorial antioxidant enzyme, has a defensive role against oxidative stress, which is believed to contribute to cancer development. This study aimed to investigate the association of PON1-L55M functional polymorphism with breast cancer risk. Material and methods: In the experimental study, blood samples were collected from 150 healthy women controls and 150 breast cancer subjects. The L55M genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Our analysis showed that the genotypes distribution is in Hardy-Weinberg equilibrium for both case and control groups. Our data revealed that there are significant associations between PON1-L55M polymorphism and breast cancer risk in homozygote (OR= 2.13, 95%CI= 1.14-4.00, p= 0.018), dominant (OR= 1.72, 95%CI= 1.07-2.76, p= 0.024), and allelic (OR= 1.55, 95%CI= 1.12-2.15, p= 0.008) models. Conclusions: Our results suggest that the PON1-L55M genetic variation could be a genetic risk factor for breast cancer risk and it could be considered as a molecular biomarker for screening of susceptible women. 相似文献
55.
Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy 下载免费PDF全文
Mauricio Pereira ManigliaAnelise RussoPatrícia Matos Biselli-ChicoteJuliana Garcia de Oliveira-CucoloGabriela Helena Rodrigues-Flemingjosé Victor -ManigliaÉrika Cristina PavarinoEny Maria Goloni-Bertollo 《Asian Pacific journal of cancer prevention》2020,21(6):1637-1644
Background/Aim: The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. Methods: The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results: The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. Conclusion: The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility. 相似文献
56.
Himiko Ogawa Koh‐ichi Nakashiro Norihiko Tokuzen Nobuyuki Kuribayashi Hiroyuki Goda Daisuke Uchida 《Cancer science》2020,111(5):1645-1651
MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether targeting these miRNAs might be useful in treatment for cancer. Functional screening for oncomiRs in a human OSCC cell line (GFP‐SAS) was carried out using the miRCURY LNA microRNA Knockdown Library – Human version 12.0. We identified a locked nucleic acid (LNA)/DNA antisense oligonucleotide against miR‐361‐3p (LNA‐miR‐361‐3p) which showed the largest degree of growth inhibition of GFP‐SAS cells. Transfection with a synthetic mimic of mature miR‐361‐3p resulted in an approximately 20% increase in the growth of GFP‐SAS cells. We identified odd‐skipped related 2 (OSR2) as a miR‐361‐3p target gene. Transfection of GFP‐SAS cells with LNA‐miR‐361‐3p caused a significant increase in the expression levels of OSR2. Cotransfection of a OSR2 3′‐UTR luciferase reporter plasmid and LNA‐miR‐361‐3p into GFP‐SAS cells produced higher levels of luciferase activity than in cells cotransfected with the LNA‐nontarget. We assessed the effect of LNA‐miR‐361‐3p on the in vivo growth of GFP‐SAS cells. We found that LNA‐miR‐361‐3p significantly reduced the size of s.c. xenografted GFP‐SAS tumors, compared to the control group treated with LNA‐NT. Finally, we observed that miR‐361‐3p is overexpressed in OSCC tissues. These results suggest that miR‐361‐3p supports the growth of human OSCC cells both in vitro and in vivo and that targeting miR‐361‐3p could be a useful therapeutic approach for patients with OSCC. 相似文献
57.
58.
目的分析1例外周血染色体核型为单纯型18三体但智力正常女性的遗传学机制。方法用G显带染色体核型分析、荧光原位杂交(fluorescence in situ hybridization,FISH)和单核苷酸多态性微阵列芯片(single nucleotide polymorphism microarray,SNP-array)技术对患者的外周血和颊粘膜细胞进行检测。结果患者的外周血染色体核型、SNP-array以及FISH检测结果均提示为47,XX,+18;颊粘膜间期细胞FISH检测结果提示为45,X合并低比例的18三体和18单体。结论胚层染色体嵌合的个体临床表现复杂,遗传学异常所造成的影响取决于相关胚层分化所形成的器官及功能。 相似文献
59.
AbstractThe aim of this study is to clarify the possible association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and pre-eclampsia in Hakka pregnant women in southern China. Pre-eclampsia and normal pregnant women were consecutively collected and MTHFR C677T genotypes were determined by the DNA sequencing method. One hundred and thirteen pre-eclampsia patients were CC homozygote (113 of 191, 59.2%), 68 of 191 (35.6%) were CT heterozygote, and 10 of 191 (5.2%) were TT homozygote, with the frequency of the T allele equal to 0.77. This is in comparison with the normal control group where 106 of 202 (52.5%) were CC homozygote, 83 of 202 (41.1%) were CT heterozygote, and 13 of 202 (6.4%) were TT homozygote, with the frequency of the T allele equal to 0.27. No statistically significant differences were observed in genotype or allele frequencies between the pre-eclampsia and normal control for the C677T polymorphism of MTHFR gene (p?>?.05). The findings of this study suggest that polymorphisms of MTHFR C677T genes were not associated with pre-eclampsia in Hakka pregnant women from southern China, but additional studies are necessary to explore the mechanisms involving it. 相似文献