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991.
Background
Rapid advances in next-generation sequencing technologies facilitate genetic association studies of an increasingly wide array of rare variants. To capture the rare or less common variants, a large number of individuals will be needed. However, the cost of a large scale study using whole genome or exome sequencing is still high. DNA pooling can serve as a cost-effective approach, but with a potential limitation that the identity of individual genomes would be lost and therefore individual characteristics and environmental factors could not be adjusted in association analysis, which may result in power loss and a biased estimate of genetic effect.Methods
For case-control studies, we propose a design strategy for pool creation and an analysis strategy that allows covariate adjustment, using multiple imputation technique.Results
Simulations show that our approach can obtain reasonable estimate for genotypic effect with only slight loss of power compared to the much more expensive approach of sequencing individual genomes.Conclusion
Our design and analysis strategies enable more powerful and cost-effective sequencing studies of complex diseases, while allowing incorporation of covariate adjustment. 相似文献992.
Liran Hiersch Joel G. Ray Jon Barrett Howard Berger Michael Geary Sarah D. McDonald Christina Diong Sima Gandhi Jun Guan Beth Murray-Davis Nir Melamed 《CMAJ》2021,193(37):E1448
Background:People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies.Methods:We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992–2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP.Results:The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7–20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57–0.97]), when compared directly.Interpretation:In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.Cardiovascular disease has been shown to be the leading cause of death among women.1–3 Classic risk factors for cardiovascular disease include obesity, diabetes mellitus, hypertension and family history of cardiovascular disease. 3 More recently, an association has been established between a history of hypertensive disorders of pregnancy (HDP) — gestational hypertension and pre-eclampsia — and future risk of cardiovascular disease.1,4–11 Consequently, some recommend using a history of HDP for cardiovascular disease risk stratification in women.3,12The leading hypothesis for the pathogenesis of HDP is that it results from abnormal placentation due to impaired trophoblast invasion,13–16 resulting in reduced placental perfusion.17–19 This, in turn, leads to abnormal secretion of the angiogenic factors soluble FMS-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng),20 which induce endothelial dysfunction and the clinical manifestations of HDP.19,21–24 The mechanisms underlying the association between HDP and future cardiovascular disease are under debate.25 One hypothesis is that HDP are merely a marker of underlying subclinical or clinical vascular risk factors that predispose a person to both HDP and future cardiovascular disease.A person who is pregnant with twins is at about 3–4 times higher risk of HDP than a person with a singleton pregnancy,26–33 with rates of 14% and 5%, respectively.34 The higher risk of HDP in twin pregnancies may be due to higher circulating sFlt1 and sEng owing to greater placental mass in twin pregnancies, 35–37 and less related to the classic vascular risk factors for HDP in a singleton pregnancy. Therefore, a logical question is whether the established higher risk of future cardiovascular disease after singleton pregnancies with HDP also occurs in twin pregnancies with HDP. Limited data are available to answer this question.38 In the current study, we aimed to test the hypothesis that the association between HDP and future cardiovascular disease is less pronounced in twin versus singleton pregnancies. 相似文献
993.
Eneyi E. Kpokiri Elizabeth Chen Jingjing Li Sarah Payne Priyanka Shrestha Kaosar Afsana Uche Amazigo Phyllis Awor Jean-Francois de Lavison Saqif Khan Jana Mier-Alpao Alberto Ong Jr Shivani Subhedar Isabelle Wachmuth Luis Gabriel Cuervo Kala M. Mehta Beatrice Halpaap Joseph D. Tucker 《PLoS medicine》2021,18(9)
994.
995.
Yuan Jin Qilin Meng Bihui Zhang Chen Xie Xue Chen Baoqing Tian Jiakang Wang Tsung-Chieh Shih Yibo Zhang Jieqiong Cao Yiqi Yang Size Chen Xinyuan Guan Xiaojia Chen An Hong 《International journal of biological sciences》2021,17(14):3689
Esophageal squamous cell carcinoma (ESCC) is one of the most common gastrointestinal tumors, accounting for almost half a million deaths per year. Cancer-associated fibroblasts (CAFs) are the major constituent of the tumor microenvironment (TME) and dramatically impact ESCC progression. Recent evidence suggests that exosomes derived from CAFs are able to transmit regulating signals and promote ESCC development. In this study, we compared different the component ratios of miRNAs in exosomes secreted by CAFs in tumors and with those from normal fibroblasts (NFs) in precancerous tissues. The mRNA level of hsa-miR-3656 was significantly upregulated in the former exosomes. Subsequently, by comparing tumor cell development in vitro and in vivo, we found that the proliferation, migration and invasion capabilities of ESCC cells were significantly improved when miR-3656 was present. Further target gene analysis confirmed ACAP2 was a target gene regulated by miR-3656 and exhibited a negative regulatory effect on tumor proliferation. Additionally, the downregulation of ACAP2 triggered by exosomal-derived miR-3656 further promotes the activation of the PI3K/AKT and β-catenin signaling pathways and ultimately improves the growth of ESCC cells both in vitro and in xenograft models. These results may represent a potential therapeutic target for ESCC and provide a new basis for clinical treatment plans. 相似文献
996.
韩国赫坎按蚊复合体3成员种核糖体DNA内转录间隔2区的比较(英文) 总被引:5,自引:0,他引:5
本文对韩国中华按蚊、雷氏按蚊和八代按蚊核糖体DNA (rDNA)内转录间隔 2区 (ITS2 )序列进行了比较研究。用PCR扩增的rDNA ITS2片段直接测序 ,每种蚊测定 3个个体 ,结果显示 :韩国中华按蚊、雷氏按蚊和八代按蚊的rDNA ITS2序列长度分别为 4 6 8bp、 4 51bp和 4 53bp ,GC含量分别为 4 4 .87%、 4 6 .2 %和 4 5.7% ,3种按蚊序列差异范围为 12 .16 %— 30 .74 %。研究表明 ,rDNA ITS2序列差异可用于韩国中华按蚊、雷氏按蚊和八代按蚊的分子鉴别。 相似文献
997.
多糖抗病毒作用研究进展Ⅰ-多糖抗病毒作用 总被引:20,自引:0,他引:20
近年来,多糖的抗病毒作用已引起极大关注。本文综述了多糖的抗病毒作用,概述了多糖构效关系、抗病毒机理、分子修饰及其与其他抗病毒药物的协同作用。多糖抗病毒药物研究前景广阔。 相似文献
998.
破伤风毒素C部分的克隆及在大肠杆菌中的表达 总被引:1,自引:0,他引:1
用CR方法从破伤风杆菌基因组DNA上坟增出破伤风毒素C部分(tetanus toxin fragment C,TTC),经测序其基因片段由1356bp组成,可编码451个氨基酸残基的多肽。将其插入原核表达载体pET-28a(+)中,并在大肠杆力BL219DE3)中表达,其表达量占可溶性总蛋白质的8.2%;SDS-PAGE和免疫印迹分析表明,TTC基因(该基因GenBank登录号为AF15482)表 相似文献
999.
Xing Kang En Xu Xingzhou Wang Lulu Qian Zhi Yang Heng Yu Chao Wang Chuanfu Ren Yizhou Wang Xiaofeng Lu Xuefeng Xia Wenxian Guan Tong Qiao 《Cell death & disease》2021,12(10)
Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.Subject terms: Gastric cancer, Tumour angiogenesis 相似文献
1000.
Yuling Fu Peng Wang Jingjing Zhao Yunke Tan Junli Sheng Shitong He Xialin Du Yulan Huang Yalong Yang Jinling Li Yuxiong Cai Yuxuan Liu Shengfeng Hu 《Cell death and differentiation》2021,28(10):2857
Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4+ T cell activation. USP12 plays an intrinsic role in promoting the CD4+ T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4+ T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4+ T cells, but not in CD8+ T cells. Our study results showed that USP12 activated CD4+ T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections.Subject terms: Ubiquitins, T cells 相似文献