全文获取类型
收费全文 | 5182篇 |
免费 | 347篇 |
国内免费 | 16篇 |
专业分类
耳鼻咽喉 | 55篇 |
儿科学 | 161篇 |
妇产科学 | 189篇 |
基础医学 | 601篇 |
口腔科学 | 180篇 |
临床医学 | 598篇 |
内科学 | 927篇 |
皮肤病学 | 98篇 |
神经病学 | 334篇 |
特种医学 | 103篇 |
外科学 | 610篇 |
综合类 | 38篇 |
一般理论 | 5篇 |
预防医学 | 535篇 |
眼科学 | 74篇 |
药学 | 328篇 |
中国医学 | 7篇 |
肿瘤学 | 702篇 |
出版年
2023年 | 27篇 |
2022年 | 41篇 |
2021年 | 102篇 |
2020年 | 89篇 |
2019年 | 102篇 |
2018年 | 137篇 |
2017年 | 117篇 |
2016年 | 105篇 |
2015年 | 137篇 |
2014年 | 188篇 |
2013年 | 273篇 |
2012年 | 328篇 |
2011年 | 358篇 |
2010年 | 230篇 |
2009年 | 170篇 |
2008年 | 337篇 |
2007年 | 325篇 |
2006年 | 354篇 |
2005年 | 289篇 |
2004年 | 281篇 |
2003年 | 264篇 |
2002年 | 256篇 |
2001年 | 87篇 |
2000年 | 63篇 |
1999年 | 59篇 |
1998年 | 61篇 |
1997年 | 59篇 |
1996年 | 51篇 |
1995年 | 48篇 |
1994年 | 36篇 |
1993年 | 40篇 |
1992年 | 67篇 |
1991年 | 55篇 |
1990年 | 46篇 |
1989年 | 35篇 |
1988年 | 29篇 |
1987年 | 32篇 |
1986年 | 27篇 |
1985年 | 31篇 |
1984年 | 42篇 |
1983年 | 25篇 |
1982年 | 22篇 |
1981年 | 17篇 |
1980年 | 24篇 |
1979年 | 20篇 |
1978年 | 14篇 |
1977年 | 9篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1968年 | 5篇 |
排序方式: 共有5545条查询结果,搜索用时 15 毫秒
21.
22.
St?le Nordg?rd Gerhard Hein Brit Kari Stene Ketil Wichman Skj?stad Joachim T Maurer 《Otolaryngology--head and neck surgery》2007,136(5):818-822
OBJECTIVE: To evaluate long-term effectiveness of palatal implants for treatment of mild to moderate obstructive sleep apnea (OSA). STUDY DESIGN: A prospective study of 26 referred patients with a pretreatment apnea-hypopnea index (AHI) of 10 to 30 and a body mass index of < or =30, representing an extended follow-up of a subset of 41 patients enrolled in previous short-term trials. RESULTS: Twenty-one of 26 patients (80.8%) experienced a decrease in AHI. Fifteen of 26 patients (57.7%) had a follow-up AHI <10 at 1 year, whereas 13 patients (50%) had a 50% or greater reduction to an AHI <10 at 1 year. Mean AHI was reduced from 16.5 +/- 4.5 at baseline to 12.5 +/- 10.5 at 3 months (P < 0.014) and to 12.3 +/- 12.7 at 1 year (P < 0.019). CONCLUSIONS: Patients initially responding to palatal implants with improved AHI maintained improvement through long-term follow-up at 1 year. 相似文献
23.
The in vitro cytotoxicity assay and the histological in vivo analysis were used to study cell-mediated immunity in the spleen of DBA/2 mice bearing subcutaneously developing P815X2 mastocytoma. Mononuclear cells separated from the spleen showed P815X2 specific cytotoxic activity between days 10 (12) and 16 following tumor inoculation. Maximal cytotoxicity was detected on days 13 and 14. In the T cell area of the spleen white pulp (C-PALS), an increase in the proportions of T lymphocytes and mononuclear phagocytes was observed on days 10 and 12 after the injection of P815X2 cells. On day 14, the T cell level in C-PALS dropped below control values, and the cellular density in the T cell area was reduced. Tumor metastases were seen in the spleen from day 14 onwards. The results indicate, that the T cell reaction in vivo was detectable in C-PALS one to two days earlier than the in vitro cytotoxicity of the spleen cells. By the time of maximal cytotoxic activity, the in vivo reaction had disappeared. 相似文献
24.
Kari Reijula Marina Leino Helena Mussalo-Rauhamaa Marjo Nikulin Harri Alenius Jari Mikkola Peter Elg Osmo Kari Soili M?kinen-Kiljunen Tari Haahtela 《Annals of allergy, asthma & immunology》2003,91(3):280-287
BACKGROUND: Alternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland. OBJECTIVE: To evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy. METHODS: Skin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens. RESULTS: The prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test. CONCLUSION: In the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens. 相似文献
25.
Erik A. Richter Bente Sonne Kari J. Mikines Thorkil Ploug Henrik Galbo 《European journal of applied physiology》1984,52(3):346-350
Summary We have previously found that during exercise net muscle glycogen breakdown is impaired in adrenodemedullated rats, as compared with controls. The present study was carried out to elucidate whether, in rats with deficiencies of the sympatho-adrenal system, diminished exercise-induced glycogenolysis in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did not influence muscle substrate concentrations. The results indicate that when glycogenolysis in exercising muscle is impeded by adrenodemedullation no compensatory increase in breakdown of triglyceride and protein in muscle or liver takes place. Thus, indirect evidence suggests that, in exercising adrenodemedullated rats, fatty acids from adipose tissue were burnt instead of muscle glycogen. 相似文献
26.
Casas KA Mononen TK Mikail CN Hassed SJ Li S Mulvihill JJ Lin HJ Falk RE 《American journal of medical genetics. Part A》2004,(4):331-339
We report a new patient with terminal deletion of chromosome 2 with breakpoint at 2q36 and five additional new patients with 2q terminal deletion with breakpoint at 2q37. Hemidiaphragmatic hernia is a novel finding in one patient with a breakpoint at 2q37.1. In comparing these patients to 60 previously reported individuals with 2q terminal deletions, certain physical abnormalities are loosely associated with positions of breakpoint. For example, facial features (e.g., prominent forehead, depressed nasal bridge, and dysmorphic ears and nose), short stature, and short hands and feet were frequent in patients with breakpoints at or proximal to 2q37.3. Reports of horseshoe kidney and Wilms tumor were limited to patients with a breakpoint at 2q37.1, and structural brain anomalies and tracheal anomalies were reported only in patients with breakpoints at or proximal to 2q37.1. Cleft palate was reported only in patients with the most proximal breakpoints (2q36 or 2q35). Neurological effects including developmental delay, mental retardation, autistic-like behavior, and hypotonia were typical in this patient population but did not stratify in severity according to breakpoint. Terminal deletion of the long arm of chromosome 2 should be considered in the infant with marked hypotonia, poor feeding, gastroesophageal reflux, and growth delay, and the older child with developmental delay, autistic behavior, and the characteristic facial and integumentary features described herein. Assignment of clinical features to specific breakpoints and refinement of predictive value may be useful in counseling. 相似文献
27.
Absence of association between an intercellular adhesion molecule 1 gene E469K polymorphism and Alzheimer's disease in Finnish patients 总被引:7,自引:0,他引:7
Mattila KM Hiltunen M Rinne JO Mannermaa A Röyttä M Alafuzoff I Laippala P Soininen H Lehtimäki T 《Neuroscience letters》2003,337(1):61-63
Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD. 相似文献
28.
Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins 总被引:3,自引:0,他引:3
Karkkainen MJ Haiko P Sainio K Partanen J Taipale J Petrova TV Jeltsch M Jackson DG Talikka M Rauvala H Betsholtz C Alitalo K 《Nature immunology》2004,5(1):74-80
Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc-/- mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/- mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development. 相似文献
29.
Tirthadipa Pradhan-Sundd Silvia Liu Sucha Singh Minakshi Poddar Sungjin Ko Aaron Bell Jonathan Franks Ian Huck Donna Stolz Udayan Apte Sarangarajan Ranganathan Kari Nejak-Bowen Satdarshan P. Monga 《The American journal of pathology》2021,191(5):885-901
Hepatocytes are highly polarized epithelia. Loss of hepatocyte polarity is associated with various liver diseases, including cholestasis. However, the molecular underpinnings of hepatocyte polarization remain poorly understood. Loss of β-catenin at adherens junctions is compensated by γ-catenin and dual loss of both catenins in double knockouts (DKOs) in mice liver leads to progressive intrahepatic cholestasis. However, the clinical relevance of this observation, and further phenotypic characterization of the phenotype, is important. Herein, simultaneous loss of β-catenin and γ-catenin was identified in a subset of liver samples from patients of progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. Hepatocytes in DKO mice exhibited defects in apical-basolateral localization of polarity proteins, impaired bile canaliculi formation, and loss of microvilli. Loss of polarity in DKO livers manifested as epithelial-mesenchymal transition, increased hepatocyte proliferation, and suppression of hepatocyte differentiation, which was associated with up-regulation of transforming growth factor-β signaling and repression of hepatocyte nuclear factor 4α expression and activity. In conclusion, concomitant loss of the two catenins in the liver may play a pathogenic role in subsets of cholangiopathies. The findings also support a previously unknown role of β-catenin and γ-catenin in the maintenance of hepatocyte polarity. Improved understanding of the regulation of hepatocyte polarization processes by β-catenin and γ-catenin may potentially benefit development of new therapies for cholestasis.A hallmark of epithelial cells is polarization, which is achieved by the orchestration of external cues, such as cellular contact, extracellular matrix, signal transduction, growth factors, and spatial organization.1 Hepatocytes in the liver show a unique polarity by forming several apical and basolateral poles within a cell.2 The apical poles of adjacent hepatocytes form a continuous network of bile canaliculi into which bile is secreted, whereas the basolateral membrane domain forms the sinusoidal pole, which secretes various components, such as proteins or drugs, into the blood circulation.3 Loss of hepatic polarity has been associated with several cholestatic and developmental disorders, including progressive familial intrahepatic cholestasis (PFIC) and primary sclerosing cholangitis (PSC).4,5 Although the molecular mechanisms governing hepatocyte polarity have been extensively studied in the in vitro systems, there is still a significant gap in our understanding of how polarity is established within the context of tissue during development or maintained during homeostasis.6,7 Similarly, the molecular pathways contributing to hepatic polarity are not entirely understood, and a better comprehension of hepatic polarity regulation is thus warranted.Previous studies have confirmed the role of hepatocellular junctions, such as tight and gap junctions, in the maintenance of hepatocyte polarity.8,9 Studies done in vitro and in vivo have shown that loss of junctional proteins, such as zonula occludens protein (ZO)-1, junctional adhesion molecule-A, and claudins, lead to impairment of polarity and distorted bile canaliculi formation.10, 11, 12, 13 In addition, proteins involved in tight junction assembly, such as liver kinase B1, are also involved in polarity maintenance.14 Among adherens junction proteins, various in vitro cell culture models have confirmed the role of E-cadherin in the regulation of hepatocyte polarity, possibly through its interaction with β-catenin.15,16 However, there is a lack of an in vivo model to study the role of adherens junction proteins in hepatocyte polarity and their misexpression contributing to various liver diseases.β-Catenin plays diverse functions in the liver during development, regeneration, zonation, and tumorigenesis.17, 18, 19 The relative contribution of β-catenin as part of the adherens junction is challenging to study because like in other tissues, γ-catenin compensates for the β-catenin loss in the liver.20,21 To address this redundancy, we previously reported a hepatocyte-specific -catenin and γ-catenin double-knockout (DKO) mouse model was reported.22 Simultaneous deletion of β-catenin and γ-catenin in mice livers led to cholestasis, partially through the breach of cell-cell junctions. However, more comprehensive understanding of the molecular underpinnings of the phenotype is needed.In the current study, prior preclinical findings of dual β-catenin and γ-catenin loss were extended to a subset of PFIC and PSC patients. In vivo studies using the murine model with hepatocyte-specific dual loss of β-catenin and γ-catenin showed complete loss of hepatocyte polarity compared to the wild-type controls (CONs). Loss of polarity in DKO liver was accompanied by epithelial-mesenchymal transition (EMT), activation of transforming growth factor (TGF)-β signaling, and reduced expression of hepatocyte nuclear factor 4α (HNF4α). Our findings suggest that β-catenin and γ-catenin and in turn adherens junction integrity, are critical for the maintenance of hepatocyte polarity, and any perturbations in this process can contribute to the pathogenesis of cholestatic liver disease. 相似文献