全文获取类型
收费全文 | 8118篇 |
免费 | 432篇 |
国内免费 | 102篇 |
专业分类
耳鼻咽喉 | 53篇 |
儿科学 | 180篇 |
妇产科学 | 646篇 |
基础医学 | 908篇 |
口腔科学 | 122篇 |
临床医学 | 928篇 |
内科学 | 1689篇 |
皮肤病学 | 79篇 |
神经病学 | 523篇 |
特种医学 | 321篇 |
外科学 | 1061篇 |
综合类 | 185篇 |
预防医学 | 408篇 |
眼科学 | 73篇 |
药学 | 592篇 |
中国医学 | 114篇 |
肿瘤学 | 770篇 |
出版年
2023年 | 38篇 |
2022年 | 95篇 |
2021年 | 175篇 |
2020年 | 92篇 |
2019年 | 145篇 |
2018年 | 246篇 |
2017年 | 166篇 |
2016年 | 155篇 |
2015年 | 208篇 |
2014年 | 243篇 |
2013年 | 381篇 |
2012年 | 568篇 |
2011年 | 579篇 |
2010年 | 374篇 |
2009年 | 315篇 |
2008年 | 492篇 |
2007年 | 556篇 |
2006年 | 538篇 |
2005年 | 442篇 |
2004年 | 378篇 |
2003年 | 319篇 |
2002年 | 311篇 |
2001年 | 264篇 |
2000年 | 277篇 |
1999年 | 202篇 |
1998年 | 65篇 |
1997年 | 65篇 |
1996年 | 64篇 |
1995年 | 38篇 |
1994年 | 56篇 |
1993年 | 37篇 |
1992年 | 131篇 |
1991年 | 96篇 |
1990年 | 75篇 |
1989年 | 53篇 |
1988年 | 58篇 |
1987年 | 48篇 |
1986年 | 52篇 |
1985年 | 35篇 |
1984年 | 45篇 |
1983年 | 16篇 |
1982年 | 11篇 |
1981年 | 17篇 |
1980年 | 14篇 |
1979年 | 16篇 |
1978年 | 11篇 |
1977年 | 15篇 |
1976年 | 10篇 |
1972年 | 7篇 |
1971年 | 10篇 |
排序方式: 共有8652条查询结果,搜索用时 15 毫秒
81.
Wei Teng Chen-Chun Lin Chung-Wei Su Po-Ting Lin Yi-Chung Hsieh Wei-Ting Chen Ming-Mo Ho Ching-Ting Wang Pei-Mei Chai Jason Chia-Hsun Hsieh Chun-Yen Lin Shi-Ming Lin 《American journal of cancer research》2022,12(4):1899
Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients. 相似文献
82.
Tracy Jiaye Lee Yu-Ching Liu Wei-An Liu Yu-Fei Lin Hsin-Han Lee Huei-Mien Ke Jen-Pan Huang Mei-Yeh Jade Lu Chia-Lun Hsieh Kuo-Fang Chung Gianni Liti Isheng Jason Tsai 《Genome research》2022,32(5):864
The ecology and genetic diversity of the model yeast Saccharomyces cerevisiae before human domestication remain poorly understood. Taiwan is regarded as part of this yeast''s geographic birthplace, where the most divergent natural lineage was discovered. Here, we extensively sampled the broadleaf forests across this continental island to probe the ancestral species’ diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages that diverged from Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Three lineages are endemic to Taiwan and six are widespread in Asia, making this region a focal biodiversity hotspot. Both ancient and recent admixture events were detected between the natural lineages, and a genetic ancestry component associated with isolates from fruits was detected in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We identified different selection patterns shaping the coding sequences of natural lineages and found fewer gene family expansion and contractions that contrast with domesticated lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.The yeast genus Saccharomyces, which includes S. cerevisiae, is a powerful model system for revealing patterns of genomic variation underlying reproductive isolation and adaptation in eukaryotic microorganisms. Surveys of population genetic data have been used in S. cerevisiae to date the origin of key domestication events (Gallone et al. 2016; Duan et al. 2018; Peter et al. 2018), to determine life cycle frequencies in nature (Tsai et al. 2008), to determine the genomic basis of adaptation at continental scale (Duan et al. 2018; Peter et al. 2018), and, more recently, to establish its geographical origin and dispersal history (Xia et al. 2017). Phylogenomic analyses of the Saccharomyces sensu stricto complex and extensive sequencing of collections across the world suggest that S. cerevisiae originated in East Asia (Duan et al. 2018; Peter et al. 2018). The 1011 Genome Project—the most broad large-scale yeast population genomic study—discovered that three wild isolates from Taiwan showed an unprecedented high genetic diversity compared with populations from the rest of the world (Peter et al. 2018). Population genomics of 266 domestic and wild isolates in China revealed six wild lineages from primeval forests. The newly identified CHN-IX group represents the most diverged lineage (Duan et al. 2018). Isolates from this group and the three Taiwanese isolates were grouped into a single lineage that showed a disjunct geographic distribution (Bendixsen et al. 2021). Although considerable knowledge is available on the biogeography and population genetics of plants and animals across continents (Whittaker et al. 2017), little is known about how eukaryotic microorganisms such as S. cerevisiae disperse, establish, reproduce, and persist in nature (Liti 2015).Most S. cerevisiae biology has been based on experiments on a handful of laboratory domesticated strains, but comprehensive analyses of the ecology and evolutionary biology of S. cerevisiae in the wild are still unavailable. In nature, S. cerevisiae have been isolated from the bark, fruits, surrounding soil, and leaves of plants belonging to several different families (Naumov et al. 2013), with early reports suggesting that the yeast is most successfully isolated from the oak family Fagaceae (Sniegowski et al. 2002; Sampaio and Gonçalves 2008; Wang et al. 2012). S. cerevisiae contains high genetic diversity in certain populations, including lineage-specific variants that display clear population structures (Barnett 1992; Wang et al. 2012; Cromie et al. 2013; Strope et al. 2015; Gallone et al. 2016; Gonçalves et al. 2016; Zhu et al. 2016; Duan et al. 2018; Legras et al. 2018; Peter et al. 2018) and explain phenotypic variance similar to common variants (Fournier et al. 2019). Samples from natural habitats tend to be homozygous diploids forming unique populations with minimal genetic admixture, whereas lineages associated with human activities were likely heterozygous, containing higher ploidy and greater genetic admixture leading to a mosaic genome makeup (Diezmann and Dietrich 2009; Liti et al. 2009; Wang et al. 2012; Almeida et al. 2015). The diverse natural lineages of S. cerevisiae present in East Asia provide an excellent opportunity to study the natural diversity of this species, which was previously believed to be fully domesticated (Fay and Benavides 2005).Taiwan is a continental shelf island with the fifth highest tree density in the world (Crowther et al. 2015). Among the 13 climate-related forests types in Taiwan, five are Fagaceae-dominated natural forests on low- and mid-elevation mountains (Li et al. 2013), thus a potentially ideal natural habitat for S. cerevisiae. Taiwan also harbors a high phylogenetic diversity of flowering plants (53 out of 64 angiosperm orders present under the APG IV classification system) (Lin and Chung 2017) and endemism compared with other oceanic islands (Hsieh 2002), raising the possibility that the associated microbial populations are genetically different from their continental counterparts. Here, we set out to characterize the intra-genetic diversity, relative abundance, and distribution of S. cerevisiae in Taiwanese forests over 4 yr of broad sampling. Our study provides novel insights of the predomestication phase of S. cerevisiae and broadens our understanding of the ecological and biogeographic implications before anthropogenic impacts. 相似文献
83.
Chen CM Chen CJ Chang CL Shyu JS Hsieh HF Harn HJ 《The Journal of surgical research》2000,94(2):84-91
BACKGROUND: This study investigated the immunophenotypic patterns of CD34, CD117 (a product of the c-kit proto-oncogene), and actin (HHF35) in benign and malignant phyllodes tumors (PTs). We correlated the expression of CD34, CD117, and actin with histopathological grade. MATERIALS AND RESULTS: We analyzed 19 cases (7 benign and 12 malignant cases) of PTs using immunohistochemical analysis. Six of 7 benign PT stromal lesions stained positively for CD34, while only 3 of 12 cases of malignant PT were focally CD34 positive (P = 0.0106). Only 1 of the 7 benign PTs stromal lesions expressed CD117. Nine of the malignant PTs were composed CD117-positive fibroblasts. This result demonstrated that CD117 expression is associated with the malignant potential of PTs (P = 0. 0106). Actin (HHF-35) expression was found in 8 of 12 cases of malignant PTs (P = 0.027), but in only 1 of 7 cases of benign PTs. Actin expression was significantly (P = 0.04) correlated to frequent mitotic activity (>5 mitoses per 10 high-power fields). The immunophenotypic markers were not related to tumor size. Additionally, we sequenced part of the juxtamembrane region of the c-kit proto-oncogene and found point mutations in two malignant PTs. CONCLUSION: Our results demonstrated that expression of CD34 was associated with benign PTs, while CD117 and actin were preferentially expressed in malignant PTs. Our results implied that these immunohistological markers might be used for the histopathological grading of PTs. 相似文献
84.
Po-Jui Chi Chung-Jen Lee Yi-Jen Hsieh Chia-Wen Lu Bang-Gee Hsu 《International journal of medical sciences》2022,19(4):729
Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. Endotoxin shock with AKI was induced by intravenous injection of 10 mg/kg LPS in C57BL6 mice with streptozotocin-induced diabetic mellitus with or without dapagliflozin treatment. Observation was done for 48 hours thereafter. In addition, NRK-52E cells incubated with LPS or dapagliflozin were evaluated for the possible mechanism. Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway. 相似文献
85.
Kwei-Jing Chen Ming-Hong Hsieh Yen-You Lin Michael Yuan-Chien Chen Ming-Yu Lien Shun-Fa Yang Chih-Hsin Tang 《International journal of medical sciences》2022,19(4):762
Oral cancer is the eighth greatest generally diagnosed cancer amongst males worldwide and the fourth most generally malignancy amongst Taiwanese males. The pro-inflammatory adipocytokine visfatin promotes tumor growth. Elevated plasma visfatin levels have been identified in patients with oral squamous cell carcinoma (OSCC), although the biological mechanisms underlying the involvement of visfatin in the pathogenesis of OSCC are not well understood. Moreover, no information is available regarding associations between visfatin polymorphisms and carcinogenic lifestyle factors with OSCC. This study, therefore, investigated the effects of four visfatin gene polymorphisms (rs11977021, rs61330082, rs2110385, and rs4730153) and carcinogenic lifestyle factors (betel nut chewing, alcohol consumption and cigarette smoking) on the risk of developing OSCC in 1,275 Taiwanese males with OSCC, and 1,195 healthy males (controls). We also examined the associations between these visfatin genotypes and OSCC histopathological prognostic factors (pathological stage, tumor status, lymph node status, and metastasis). We found that compared with subjects with the CC genotype of SNP rs11977021, those with the CT+TT genotype were less likely to progress OSCC. In addition, an association was found between the rs4730153 variant and lymph node metastasis in the OSCC cohort. 相似文献
86.
87.
88.
Pagona Lagiou Chung-Cheng Hsieh Evangelia Samoli Areti Lagiou Biao Xu Guo-Pei Yu Sagano Onoyama Lucy Chie Lars J. Vatten Hans-Olov Adami Dimitrios Trichopoulos Michelle A. Williams 《Annals of epidemiology》2013,23(11):669-673
PurposePlacental weight has been associated with mammographic pattern and coronary heart disease in the adult offspring, but the mechanisms are unknown. We evaluated the associations of maternal and cord blood hormones with placental weight in normal pregnancies.MethodsProspective study of 167 normal singleton pregnancies in Boston, USA and 256 in Shanghai, China. Maternal hormone levels at the 27th gestational week were available for all pregnancies. Cord blood measurements were available for 86 pregnancies in Boston and 104 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with placental weight were calculated.ResultsMaternal levels of estriol, testosterone, and progesterone (P < .05) were positively associated with placental weight. There was no such evidence for adiponectin, prolactin, and insulin-like growth factor (IGF)-I. Cord blood steroids tended to be inversely associated with placental weight, the results being statistically significant for testosterone (P < .05). There was a marginally significant positive association of cord blood IGF-I with placental weight. Reported results were adjusted for study center.ConclusionsPlacental weight appears to be positively correlated with maternal steroids. Its correlation with cord blood steroids, however, appears inverse, compatible with negative feedback mechanisms. There is also a suggestion for placental weight to be positively associated with cord blood IGF-I. 相似文献
89.
90.