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51.
Analysis of microdissected prostate tissue with ProteinChip arrays--a way to new insights into carcinogenesis and to diagnostic tools 总被引:9,自引:0,他引:9
Wellmann A Wollscheid V Lu H Ma ZL Albers P Schütze K Rohde V Behrens P Dreschers S Ko Y Wernert N 《International journal of molecular medicine》2002,9(4):341-347
Prostate carcinomas are one of the most common malignancies in western societies. The pathogenesis of this tumor is still poorly understood. These tumors present with two characteristic features: epithelial-mesenchymal interactions, which play a pivotal role for tumor development and most of clinically manifest cancers arise in prostate proper compared to a minority of tumors which develop in the transitional zone. Deciphering the epithelial-mesenchymal cross talk and identification of molecular pecularities of the sub-populations of cells in different zones can therefore help understanding carcinogenesis and development of new, non-invasive tools for the diagnosis and prognosis of prostate carcinomas which has remained a challenge until today. A ProteinChip array technology (SELDI = surface enhanced laser desorption ionization) has been developed recently by Ciphergen Biosystems enabling analysis and profiling of complex protein mixtures from a few cells. This study describes the analysis of approximately 500-1000 freshly obtained prostate cells by SELDI-TOF-MS (surface enhanced laser desorption ionization time-of-flight mass spectrometry). Pure cell populations of stroma, epithelium and tumor cells were selected by laser assisted microdissection. Multiple specific protein patterns were reproducibly detected in the range from 1.5 to 30 kDa in 28 sub-populations of 4 tumorous prostates and 1 control. A specific 4.3 kDa peak was increased in the prostate tumor stroma compared to normal prostate proper and transitional zone stroma and increased in prostate tumor glands compared to normal prostate proper and transitional zone glands. Coupling laser assisted microdissection with SELDI provides tremendous opportunities to identify cell and tumor specific proteins to understand molecular events underlying prostate carcinoma development. It underlines the vast potential of this technology to better understand pathogenesis and identify potential candidates for new specific biomarkers in general which could help to screen for and distinguish disease entities, i.e. between clinically significant and insignificant carcinomas of the prostate. 相似文献
52.
53.
Supernumerary marker chromosomes (SMC) can be associated with both normal and abnormal phenotypes. In addition, SMC are found at higher frequency in males with infertility. We identified a SMC, characterized as a del(15)(q11.2) chromosome, in a phenotypically normal male. Using fluorescence in situ hybridization (FISH), we examined the segregation of the del(15) chromosome in sperm from this patient. Only 6.23% of sperm nuclei showed disomy using a chromosome 15 alpha-satellite FISH probe, instead of the expected 50%. In addition, FISH analysis showed no increase for non-disjunction of chromosome 18, excluding an interchromosomal effect for this chromosome. The significant decrease in sperm bearing the del(15) may be due to tissue-specific mosaicism or a result of some form of selection against the del(15) during spermatogenesis. This finding provides a basis for the observation that SMC(15) are less likely to be inherited from a paternal carrier. 相似文献
54.
Recent evidence points to the fact that osteoclasts are derived from mononuclear cells of hematopoietic bone marrow. In this study we have examined the formation of osteoclasts from mononuclear cells in vitro. The mononuclear cells were isolated after 7 days from cultures of mouse bone marrow cells. The isolated cells were co-cultured with osteoclast-free, fetal-mouse calvaria. After 10 to 14 days of co-culture, multinucleated cells which have all the characteristics of osteoclasts were found in juxtaposition to seams of woven bone. These data strongly suggest that bone marrow mononuclear cells, when suitably induced, can give rise to osteoclasts in vitro. 相似文献
55.
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
56.
Yoshinori Seko Shigeru Ishiyama Toshiro Nishikawa Takeshi Kasajima Michiaki Hiroe Shin Suzuki Sugao Ishiwata Sachio Kawai Yuetsu Tanaka Miyuki Azuma Tetsuji Kobata Hideo Yagita Ko Okumura Ryozo Nagai 《Cardiovascular pathology》2002,11(3):166-170
BACKGROUND: T-cell-mediated myocardial damage is known to be involved in acute myocarditis and dilated cardiomyopathy. Recently, we found that tumor necrosis factor (TNF) ligand superfamily costimulatory molecules, especially 4-1BBL, played an important role in the myocardial damage of murine acute viral myocarditis. METHODS AND RESULTS: To investigate the roles for CD27L, CD30L, OX40L and 4-1BBL, which belong to TNF ligand superfamily, in the development of acute myocarditis and dilated cardiomyopathy, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and dilated cardiomyopathy. We also examined expression of the receptors for these molecules, CD27, CD30, OX40 and 4-1BB, which belong to TNF receptor superfamily, on the infiltrating cells. Strong expression of CD27L, CD30L and 4-1BBL and weak to moderate expression of OX40L was found in the cardiac myocytes of patients with acute myocarditis. Moderate expression of CD27L, CD30L and 4-1BBL and weak expression of OX40L was found on the cardiac myocytes of patients with dilated cardiomyopathy. Most of the infiltrating cells expressed CD27, CD30 and 4-1BB and a part of the infiltrating cells expressed OX40. CONCLUSIONS: Our findings suggest that expression of TNF ligand superfamily costimulatory molecules on cardiac myocytes may play a role in the cell-mediated myocardial damage in patients with acute myocarditis and dilated cardiomyopathy as in murine viral myocarditis. 相似文献
57.
F. W. S. Ko H. Y. Wang† G. W. K. Wong‡ T. F. Leung‡ D. S. C. Hui D. P. S. Chan N. S. Zhong† C. K.W. Lai 《Clinical and experimental allergy》2005,35(11):1449-1456
BACKGROUND: Asthma is a common chronic disease and information on its management practices at the community level is helpful in identifying problems and improving asthma care. OBJECTIVE: To assess the severity status and management of the asthma symptom of wheeze of children at the community level in Hong Kong (HK) and Guangzhou (GZ). METHODS: Cross-sectional study of children aged 10 years using the International Study of Asthma and Allergic disease in Childhood (ISAAC Phase II protocol). Asthma management and lung function were assessed in 178 (98 from HK and 80 from GZ) randomly selected children with wheeze over the past 12 months. RESULTS: Eighty-three percent, 11%, 6% and 0% of children suffered from intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively, according to the frequency of their symptoms. Addition of spirometric parameter only changed the asthma severity classification in 2.8% of children. Medications were used by 30.6% and 71.3% of children for wheeze in HK and GZ, respectively. In HK, inhaled beta(2)-agonist (73.3% among the drug users) was the commonest medication used followed by inhaled corticosteroid (ICS) (23.3%). In GZ, inhaled beta(2)-agonist was used by 75.4% of children, but use of ICS (26.3%), oral beta(2)-agonist (26.3%), oral theophylline (45.6%), oral ketotifen (36.8%) and oral steroid (35.1%) were also common. ICS was only used by 11.4% of children with persistent asthma. Ten percent and 18.7% of children in HK and GZ, respectively, had emergency department visits, while 16.3% and 11.6% of children in HK and GZ, respectively, had missed school secondary to asthma over the past 1 year. CONCLUSIONS: Most children in the community had intermittent asthma and addition of lung function to symptoms did not significantly affect classification of asthma severity. Significant morbidity was seen even in this group of children with mostly intermittent and mild persistent asthma. 相似文献
58.
Hanfei Xu Karen Schwander Michael R. Brown Wenyi Wang R. J. Waken Eric Boerwinkle L. Adrienne Cupples Lisa de las Fuentes Diana van Heemst Oyomoare Osazuwa-Peters Paul S. de Vries Ko Willems van Dijk Yun Ju Sung Xiaoyu Zhang Alanna C. Morrison D. C. Rao Raymond Noordam Ching-Ti Liu 《European journal of human genetics : EJHG》2021,29(5):839
Recent studies consider lifestyle risk score (LRS), an aggregation of multiple lifestyle exposures, in identifying association of gene-lifestyle interaction with disease traits. However, not all cohorts have data on all lifestyle factors, leading to increased heterogeneity in the environmental exposure in collaborative meta-analyses. We compared and evaluated four approaches (Naïve, Safe, Complete and Moderator Approaches) to handle the missingness in LRS-stratified meta-analyses under various scenarios. Compared to “benchmark” results with all lifestyle factors available for all cohorts, the Complete Approach, which included only cohorts with all lifestyle components, was underpowered due to lower sample size, and the Naïve Approach, which utilized all available data and ignored the missingness, was slightly inflated. The Safe Approach, which used all data in LRS-exposed group and only included cohorts with all lifestyle factors available in the LRS-unexposed group, and the Moderator Approach, which handled missingness via moderator meta-regression, were both slightly conservative and yielded almost identical p values. We also evaluated the performance of the Safe Approach under different scenarios. We observed that the larger the proportion of cohorts without missingness included, the more accurate the results compared to “benchmark” results. In conclusion, we generally recommend the Safe Approach, a straightforward and non-inflated approach, to handle heterogeneity among cohorts in the LRS based genome-wide interaction meta-analyses.Subject terms: Genetics, Risk factors 相似文献
59.
Kim MS Lee J So HS Lee KM Jung BH Chung SY Moon SR Kim NS Ko CB Kim HJ Kim YK Park R 《Immunopharmacology and immunotoxicology》2001,23(1):55-66
Mistletoe lectin-II, a major composition of Korean mistletoe (Viscum album coloratum), is known as a potent apoptosis inducer. The previous research has demonstrated that Korean mistletoe lectin-II induces apoptosis via c-Jun N terminal kinase (JNK) activation in human myeloid U937 cells. The purpose of this research is to prove the synergistic action of mistletoe lectin-II and interferon-γ (IFN-γ) in the apoptotic cytotoxicity of U937. When U937 cells were treated with mistletoe lectin-II after being differentiated by IFN-γ, the proteolytic activity of caspase-3 and 9 was markedly elevated and that of caspase-8 was prolonged for 18 hr. The activation of caspase-3-like protease requires the earlier cleavage of poly(ADP-ribose) polymerase(PARP). Caspase-1 was, however, not activated during the resting phase and nor in IFN-γ-differentiated U937 cells. Western blot analysis revealed that, in IFN-γ-differentiated U937 cells, the expression of Fas (CD95/APO-1) & Fas ligand(FasL) increases the apoptotic sensitivity against Mistletoe lectin-II. Fas (CD95/APO-1) & FasL were not significantly induced solely by mistletoe lectin-II. Furthermore the activity of JNK1 in U937 cells was also markedly increased with IFN-γ-differentiation, compared to that of the control. These results suggest that the IFN-γ-differentiation of U937 cells increases the susceptibility to mistletoe lectin-II-induced apoptosis. 相似文献
60.
Chia-Ying Liu Chih-Cheng Lai Hsiu-Tzy Chiang Min-Chi Lu Ling-Fang Wang Tsai-Ling Tsai Mei-Yu Kang Yi-Ni Jan Yi-Ting Lo Wen-Chien Ko Shu-Hui Tseng Chun-Ming Lee Po-Ren Hsueh 《Journal of microbiology, immunology, and infection》2019,52(1):62-74