全文获取类型
收费全文 | 44587篇 |
免费 | 3899篇 |
国内免费 | 3068篇 |
专业分类
耳鼻咽喉 | 356篇 |
儿科学 | 695篇 |
妇产科学 | 630篇 |
基础医学 | 5532篇 |
口腔科学 | 712篇 |
临床医学 | 5927篇 |
内科学 | 7348篇 |
皮肤病学 | 480篇 |
神经病学 | 2777篇 |
特种医学 | 1436篇 |
外国民族医学 | 17篇 |
外科学 | 4887篇 |
综合类 | 6779篇 |
现状与发展 | 5篇 |
一般理论 | 7篇 |
预防医学 | 2676篇 |
眼科学 | 1218篇 |
药学 | 4440篇 |
31篇 | |
中国医学 | 1857篇 |
肿瘤学 | 3744篇 |
出版年
2024年 | 140篇 |
2023年 | 667篇 |
2022年 | 1711篇 |
2021年 | 2179篇 |
2020年 | 1597篇 |
2019年 | 1533篇 |
2018年 | 1602篇 |
2017年 | 1376篇 |
2016年 | 1288篇 |
2015年 | 1918篇 |
2014年 | 2390篇 |
2013年 | 2162篇 |
2012年 | 3225篇 |
2011年 | 3452篇 |
2010年 | 2065篇 |
2009年 | 1704篇 |
2008年 | 2338篇 |
2007年 | 2394篇 |
2006年 | 2238篇 |
2005年 | 2239篇 |
2004年 | 1530篇 |
2003年 | 1479篇 |
2002年 | 1254篇 |
2001年 | 1113篇 |
2000年 | 1124篇 |
1999年 | 1234篇 |
1998年 | 670篇 |
1997年 | 732篇 |
1996年 | 552篇 |
1995年 | 490篇 |
1994年 | 434篇 |
1993年 | 301篇 |
1992年 | 367篇 |
1991年 | 325篇 |
1990年 | 277篇 |
1989年 | 247篇 |
1988年 | 226篇 |
1987年 | 193篇 |
1986年 | 176篇 |
1985年 | 128篇 |
1984年 | 73篇 |
1983年 | 78篇 |
1982年 | 49篇 |
1981年 | 55篇 |
1980年 | 31篇 |
1979年 | 46篇 |
1978年 | 24篇 |
1977年 | 29篇 |
1974年 | 18篇 |
1973年 | 16篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Patients with nonalcoholic fatty liver disease (NAFLD) have symptoms of a gut microbiota disorder with abnormal amino acid and glycolipid metabolism. This study was designed to analyze the characteristics of gut microbiota in patients with NAFLD, predict the gut microbiota phenotype, explore its role in the diagnosis of NAFLD, and establish its significance in disease progression.The characteristics of the gut microbiota in NAFLD patients (n = 28, 45.8 ± 14.2 years, male/female = 18/10) and healthy subjects (n = 20, 49.6 ± 4.8 years, male/female = 14/6) during March–May 2020 were analyzed using 16S rRNA sequencing technology and the phenotypes with large differences were predicted using the Tax4Fun method. The metabolites in the fecal samples of the patients were analyzed using mass spectrometry, and their correlation with different microorganisms was examined. The accuracy of the gut microbiota in diagnosing NAFLD was investigated by receiver operating characteristic curve analysis.We found that the microbial diversity and Bacteroides/Firmicutes (BF) ratio changed significantly (P < .05) in the feces of NAFLD patients. Phenotypic prediction showed that there were significant differences in the phenotypes of amino acid, glucose, and lipid metabolism of gut microbiota in the NAFLD group (P < .05). receiver operating characteristic curve analysis revealed that combination of Bacteroides and the BF ratio resulted in 88% and 100% sensitivity and specificity, respectively, when used for NAFLD diagnosis. Metabolomics and bioinformatics analysis revealed changes in the metabolism of nicotinate, nicotinamide, and pyrimidine; signaling pathways of calcium and oxytocin; pancreatic secretion with metabolites such as uracil, xanthine, and biliverdin; and enzymes such as xanthine dehydrogenase and xanthine oxidase (P < .05).Therefore, the phenotypic changes may be a potential marker for NAFLD and we considered that a combined analysis of Bacteroides and BF ratio had good diagnostic accuracy for NAFLD. 相似文献
992.
Anh-Hoa Nguyen Pham Kim-Oanh Bui Thi Mai-Huong Nguyen Thi Diem-Ngoc Ngo Nakayuki Naritaka Hiroshi Nittono Hisamitsu Hayashi Trang Thi Dao Kim-Huong Thi Nguyen Hoai-Nghia Nguyen Hoa Giang Hung-Sang Tang Tat-Thanh Nguyen Dinh-Kiet Truong Minh-Dien Tran 《Medicine》2022,101(25)
Rationale:Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death.Patient concerns:Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients.Diagnoses:The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr).Interventions:Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d.Outcomes:The patients’ symptoms, signs, and primary bile acids levels improved significantly.Lessons:Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes. 相似文献
993.
Zhongying Zhang Xiang Gu Zhe Tang Shaochen Guan Hongjun Liu Xiaoguang Wu Yan Zhao Xianghua Fang 《Journal of clinical hypertension (Greenwich, Conn.)》2022,24(7):825
The associations of blood pressure components with cardiovascular risks and death remain unclear, and the definition of wide pulse pressure (PP) is still controversial. Using data from 1257 participants without a history of cardiovascular disease, who were followed for 4.84 years, we performed multivariable Cox regression analyses to assess how systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP contribute to risks of cardiovascular events and all‐cause death. Among all participants, SBP and PP were significantly associated with the risks of cardiovascular events and all‐cause death (all p < .05). DBP was not significantly associated with the risk of all‐cause death; rather, it was only associated with a marginally significant 1% increased risk for cardiovascular events (p = 0.051). In participants aged < 65 years, DBP was significantly associated with a 3% increased risk for cardiovascular events (hazard ratio [HR]: 1.03, 95% confidence interval [95% CI]: 1.01–1.06). The association between PP and cardiovascular events appeared to be J‐shaped in comparison to participants with the lowest‐risk PP (50–60 mmHg), with adjusted HRs of 1.71 (95% CI: 1.03–2.85), 1.63 (95% CI: 1.00–2.68), and 2.13 (95% CI: 1.32–3.43) in the <50, 60.0–72.5, and ≥72.5 mmHg subgroups, respectively. The optimal cutoff points of a wide PP for predicting the risks of cardiovascular events and all‐cause death were 70.25 and 76.25 mmHg, respectively. SBP and PP had a greater effect on cardiovascular risk, whereas DBP independently influenced cardiovascular events in middle‐aged participants. Considerable PP alterations should be avoided in antihypertensive treatment. 相似文献
994.
Buzhou Xu Hao Tang Yiming Weng Valerie Sloane Jones Shuhong Luo Chih Yun Cho Yongping Lin Jianmin Fang Xuedong Song RuoPan Huang 《Journal of clinical laboratory analysis》2022,36(7)
BackgroundThe spread of COVID‐19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15‐minute time‐resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS‐CoV‐2 spike protein receptor‐binding domain (S1‐RBD).ObjectivesOur objective was to develop an efficient method of detecting SARS‐CoV‐2 within 15 min of sample collection.MethodsWe constructed and evaluated a portable, disposable lateral flow device, which detected the S1‐RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1‐RBD, which can be captured by an automated TRF instrument.ResultsThe TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1‐RBD antigen.ConclusionThe new S1‐RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR‐based methodology in nasopharyngeal swab samples, showing that the detected S1‐RBD antigen levels correlate with SARS‐CoV‐2 virus load. Therefore, the new TRF lateral flow test for S1‐RBD has potential application in point‐of‐care settings. 相似文献
995.
Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Eucommia ulmoides (EU) is a kidney-tonifying Chinese medicine that has been applied to treat RA for decides. The present study aims to explore pharmacological mechanisms of EU against RA using network pharmacology approach. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of EU, and their relative targets were fished from UniProt database. RA-related targets were screened from GeneCards database and DisGeNET database. The overlapping genes between EU and RA were identified by Venn diagram, and further analyzed for protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). Fifty active ingredients were identified in EU, and corresponded to 207 targets. Meanwhile, 499 targets were closely associated with RA development. A total of 50 overlapping genes between EU and RA were identified, which were regarded as therapeutically relevant. GO enrichment analysis indicated that EU exerted antiRA effects depending on regulating multiple biological processes including inflammatory response, oxidative stress, cell apoptosis and matrix catabolism. Several key pathways such as TNF pathway, IL-17 pathway, T cell receptor pathway, NOD-like receptor pathway and Toll-like receptor pathway, were involved in the above biological processes. Network pharmacology revealed that EU exerts therapeutic effects on RA through multi-ingredients, multi-targets and multi-pathways, which provides basis for its clinical application and promising directions for subsequent research. 相似文献
996.
Li Yingxian Chen Wei Zhao Linchun Zhang Ji-Quan Zhao Yonglong Li Chun Guo Bing Tang Lei Yang Yuan-Yong 《RSC advances》2022,12(32):20550
Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry and the construction of this motif with high atom economy is the focus of the current research. Specifically, N-methyl amides are valuable building blocks in natural products and pharmaceutical science. Due to the volatile nature of methyl amine, the generation of N-methyl amides using simple acids with high atom economy is rare. Herein, we disclose an atom economic protocol to prepare this valuable motif under DABCO/Fe3O4 cooperative catalysis. This protocol is operationally simple and compatible with a range of aliphatic and (hetero)aromatic acids with very good yields (60–99%). Moreover, the Fe3O4 can be easily recovered and high efficiency is maintained for up to ten cycles.The generation of N-methyl amides using simple acids with high atom economy is rare owning to the volatile nature of methyl amine. Herein, an atom economic protocol was disclosed to prepare this valuable motif under DABCO/Fe3O4 cooperative catalysis.Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry.1 It is widely distributed in natural products, synthetic drugs and functional polymers, and is also the key chemical connection in proteins.2 It has been shown that amide bond formation alone accounts for 65% of all preliminary screening reactions in the pharmaceutical industry.3 This means the generation of amide bonds with high atom efficiency is of high practical importance. And not surprisingly, ‘amide formation avoiding poor atom economy reagents’ was voted as the top challenge for organic chemistry by the ACS Green Chemistry Institute in 2007.3From synthetic point of view, the ideal way to produce amide bonds would be the direct coupling of readily available carboxylic acids and amines, but this process is thermodynamically unfavourable due to the formation of the corresponding carboxylate-ammonium salt,4 therefore, stoichiometric amount of coupling reagents, such as DCC, DIC, EDCI, HATU, HBTU, HCTU, SOCl2, BOP, acid chloride etc, are generally required to sidestep thermal conditions for amide bond formation.5 These reagents are highly successful, but the process generally suffers from poor atom economy and side products removal issue especially in the large-scale applications.5 To overcome these drawbacks, “nonclassical” amide bonds formation routes were investigated.6 In these processes, the catalyst takes the role of a coupling reagent in generating an active ester suitable for amidation in a waste-free manner. However, these processes have not been applied in the preparation of N-methyl amides, probably because the methyl amine was delivered in its hydrochloride salt, alcoholic or aqueous form due to its volatile nature.On a different note, N-methyl amides are extensively presented in numerous natural products and pharmaceutical molecules, as shown in Fig. 1,7 and the methylation of amides is a promising way to improve the pharmacological property of molecules.8 However, the synthesis of N-methyl amides compounds relies heavily on non-catalytic approaches.5,9 Catalytic approaches were also investigated by Hisaeda,10 Kundu,11 Li,12 Guo,13 Yu,14 Maruoka,15 Wang,16 Chen,17 Lamaty18 and their co-workers starting from nitriles, primiary amides, aldoximes, aldehydes, lignin, carbamoylsilane and alcohols. Until recently, Thakur,19 Marce,20 Sadeghzadeh21 and their co-workers developed elegant N-methyl amidation approach starting from carboxylic acids under nano-MgO, diatomite Earth@IL/ZrCl4 and Mg(NO3)2·6H2O catalysis respectively, while limitations like poor substrate scope or sophisticated tailored catalyst still persist. Mindful of all the above issues, developing an N-methyl amidation process of simple carboxylic acids, which is still of great challenge in synthesis, and establishing a broad (hetero)aryl scope with high atom economy from commercial available reagents and catalysts were critical considerations in this study. Moreover, the significance of N-methyl amides combined with our interests in the development of green synthetic approaches motivated us to explore the direct coupling of the carboxylic acids and isothiocyanates. To the best of our knowledge, this is the first successful work using isothiocyanatomethane to prepare N-methyl amides.Open in a separate windowFig. 1Marketed drugs bearing N-methyl amide group.Our initial investigation begins with phenylacetic acid and isothiocyanatomethane as model substrate for condition optimization. Using acetonitrile as solvent, only trace amount of product was detected under catalyst free or p-toluenesulfonic acid (PTSA) catalysis conditions ( Entry Additive Time (h) Catalyst Yield (%) 1 — 24 — 5 2 — 24 PTSA — 3 — 48 TEA 17 4 — 48 DBU 45 5 — 48 DMAP 43 6 — 48 DBN 51 7 — 48 DABCO 65 8 LiBr 48 DABCO 71 9 Mn(OAc)2 48 DABCO 75 10 MnO 48 DABCO 79 11 MgO 48 DABCO 88 12 Al2O3 48 DABCO 85 13 Fe3O4 48 DABCO 98 14 Fe3O4 24 DABCO 75 15b Fe3O4 48 DABCO 80