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51.
52.
Patricia Sarlos Dalma Varszegi Veronika Csongei Lili Magyari Luca Jaromi Lajos Nagy Bela Melegh 《World journal of gastroenterology : WJG》2014,20(1):219-227
AIM:To study the inflammatory bowel disease-5 locus(IBD5)and interleukin-23 receptor(IL23R)gene variants in UC patients and test for gene-gene interaction.METHODS:The study population(n=625)was comprised of 320 unrelated ulcerative colitis(UC)patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus(IGR2198a1 rs11739135,IGR2096a1 rs12521868,IGR2230a1 rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367)and two of the IL23R gene(rs1004819,rs2201841)were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency(P=0.032)in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers(P=0.004,OR=1.606;95%CI:1.160-2.223)and the SNP rs2201841 for homozygotes(P=0.030,OR=1.983;95%CI:1.069-3.678).Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a1 C or IGR2096a1 T allele,the highest OR was calculated in the presence of SLC22A4T allele(P=0.005,OR=2.015;95%CI:1.230-3.300).There was no association with UC for any combinations of rs1004819 and IGR2230a1.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD. 相似文献
53.
Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency
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Stefan D. Anker Stefan Schroeder Dan Atar Jeroen J. Bax Claudio Ceconi Martin R. Cowie Adam Crisp Fabienne Dominjon Ian Ford Hossein‐Ardeschir Ghofrani Savion Gropper Gerhard Hindricks Mark A. Hlatky Richard Holcomb Narimon Honarpour J. Wouter Jukema Albert M. Kim Michael Kunz Martin Lefkowitz Chantal Le Floch Ulf Landmesser Theresa A. McDonagh John J. McMurray Bela Merkely Milton Packer Krishna Prasad James Revkin Giuseppe M.C. Rosano Ransi Somaratne Wendy Gattis Stough Adriaan A. Voors Frank Ruschitzka 《European journal of heart failure》2016,18(5):482-489
Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. 相似文献
54.
Phylogenetic analysis of rabbit haemorrhagic disease and European brown hare syndrome viruses by comparison of sequences from the capsid protein gene 总被引:10,自引:0,他引:10
N. Nowotny C. Ros Bascuñana A. Ballagi-Pordaány D. Gavier-Wideén M. Uhleén S. Belaák 《Archives of virology》1997,142(4):657-673
Summary. A 398 bp fragment of the capsid protein (VP60) gene of 39 clinical samples of rabbit haemorrhagic disease virus (RHDV) and
17 of European brown hare syndrome virus (EBHSV), collected between 1981 and 1995 from 17 countries, was amplified by PCR
and directly sequenced. The alignment of the nucleotide sequences and the subsequently constructed phylogenetic tree clearly
separated RHDV from EBHSV as phylogenetic entities. The nucleotide homology rates between the RHDV and EBHSV groups ranged
between 52.6% and 60.0%. The homology rates within the groups were much higher, 89.4% to 100% for the RHDV samples, and 89.4%
to 100% for the EBHSV specimens. No intermediate viruses were found. Despite the high homology, three main branches could
be identified in the phylogenetic tree of the RHDV samples, corresponding to the epizootiological data, while the EBHSV dendrogram
did not show such well defined branches. The present results support the classification of RHDV and EBHSV as two distinct
members of the Caliciviridae family. Nevertheless, a comparison with previously determined sequences of other caliciviruses shows that RHDV and EBHSV are
more closely related to each other than to any other calicivirus.
Received July 30, 1996 Accepted October 25, 1996 相似文献
55.
Bela Goyal Krishan Kumar Dheeraj Gupta Ritesh Agarwal Romica Latawa Javaid Ahmad Sheikh Indu Verma 《Diagnostic microbiology and infectious disease》2014
Tuberculosis (TB) continues to be a major health problem due to lack of accurate, rapid, and cost-effective diagnostic tests. Serodiagnostic tests incorporating highly specific region of difference (RD) antigens (early secretory antigenic target 6 [ESAT-6], culture filtrate protein 10 [CFP-10], culture filtrate protein 21 [CFP-21], and mycobacterial protein from species tuberculosis 64 [MPT-64]) have recently been shown to be promising for specific diagnosis of TB in our lab. However, only few studies have reported the use of synthetic peptides of RD antigens, and none has used them to differentiate TB from sarcoidosis, a close mimic of smear-negative pulmonary TB (PTB) with entirely different management. The present study was conducted with an aim to study the utility of B-cell epitopes based peptides of RD1 (ESAT-6, CFP-10) and RD2 (CFP-21, MPT-64) antigens for immunodiagnosis of PTB for which sputum smear-positive PTB patients, sputum smear-negative PTB patients, sarcoidosis patients, and healthy controls (n = 24/group) were recruited. Bioinformatic software Bcepred was used to predict linear B-cell epitopes, using physico-chemical properties on a non-redundant dataset. Seven peptides as representative B-cell epitopes of ESAT-6, CFP-10, CFP-21, and MPT-64 were evaluated as targets of the antibody responses in TB patients and controls by enzyme-linked immunosorbent assay (ELISA). The current study showed sensitivity with individual peptides ranging from 37.5% to 83.3% for smear positive, 25% to 58.3% for smear negative as compared to 4.16% to 20.8% for sarcoidosis. Four out of 7 peptides that showed higher reactivity with TB patients and better discrimination from sarcoidosis patients representing ESAT-6, CFP-10, CFP-21, and MPT-64 were selected for multiepitope ELISA. The combination of peptides yielded 83.3% sensitivity for smear positive, 62.5% for smear negative, and only 4.16% for sarcoidosis. The specificity, however, for all the peptides/combination was 100%. Combination of peptides has proven to be better than individual peptides as per the latest criteria of the World Health Organization according to which a test that can replace smear microscopy with sensitivity of >90% for smear-positive patients and >65% for smear-negative TB patients with a specificity >95%, and thus, the present study suggests that a test based on combination of peptides selected from mycobacterial RD1 and RD2 antigens could be important for promoting an early diagnosis and management of otherwise difficult to diagnose smear-negative PTB patients. Moreover, it can also be used to discriminate sarcoidosis from PTB, thus preventing the misdiagnosis and mismanagement. 相似文献
56.
Rene Ratschmann Milen Minkov Ana Kis Christina Hung Tony Rupar Adolf Mühl Brian Fowler Ebba Nexo Olaf A. Bodamer 《Molecular genetics and metabolism》2009,98(3):285-288
Transcobalamin II deficiency (# MIM 275350) is a rare, recessively inherited disorder of cobalamin transport that leads to intracellular cobalamin depletion with secondary impairment of methionine synthetase and methyl-malonyl CoA mutase activities. Affected individuals may suffer from long-term neurological sequelae if therapy with intramuscular hydroxocobalamin is not initiated promptly. We report two sisters with complete absence of transcobalamin due to homozygosity for a novel mutation (c.insC110) in the TCN2 gene that leads to a premature stop codon and non-functional protein. The older sister, now 4.5 years old, presented at 6 weeks of age with pancytopenia, protein losing enteropathy and a rapidly declining clinical course. Prompt therapy with 1 mg hydroxocobalamin/day led to full recovery within days. Her now 1.5 year old sister was diagnosed shortly after birth and was started on hydroxocobalamin prior to onset of clinical symptoms. Interestingly, urinary methylmalonic acid excretion was increased significantly during the first days of life suggesting that functional cobalamin deficiency is present also during fetal life, although not giving rise to clinical symptoms until well after birth. 相似文献
57.
Vikas Sinha Rizwan Memon Devang Gupta Bela Prajapati Vadisha Bhat Yogesh More 《Indian journal of otolaryngology and head and neck surgery》2007,59(3):211-214
Inhalation of foreign body into the tracheobronchial tree is a medical emergency sometimes resulting into sudden death. The current mortality rate due to foreign body inhalation ranges from 0% to 1.8%. Children with or without positive history of aspiration were examined and diagnosis was made on the basis of history, clinical findings, radiological evaluation and strong index of suspicion. A review of 30 cases of suspected foreign body aspiration revealed, children between 6 months were found to be very vulnerable to aspiration. Majority of children were boys. 80% of the patients had positive history of inhalation. Only 50% of the patients presented immediately i.e. within 24 hours after aspiration. Common symptoms were cough and respiratory distress. Decreased air entry was the significant clinical sign (50%). Obstructive emphysema and mediastinal shift were found in the majority of cases (50%). Rigid bronchoscopy under general anaesthesia and patient ventilating using a jet ventilator is a very safe and effective technique. 相似文献
58.
The possibilities and the difficulties of prenatal ultrasonography in detecting fetal renal abnormalities are discussed in this review article. The consequences of prenatally diagnosed uropathies are: intrauterine surgery, termination of pregnancy, induction of premature labour and an optimal preparation for the immediate postnatal diagnosis and management. 相似文献
59.
Bodey B 《Expert opinion on therapeutic targets》2002,6(1):57-72
The thymus provides an optimal cellular and humoral microenvironment for a cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide, called thymotaxin, by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular microenvironment. The thymic RE cells are functionally specialised based on their intrathymic location and this differentiation is modulated by various interaction signals of differentiating Thymocytes and other nonlymphatic, haematopoietic stem cells. The subcapsular, endocrine, RE cell layer is comprised of cells filled with periodic acid Shiff's-positive granules, which also express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. Thymic nurse cells also produce thymosins beta 3 and beta 4 and display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+ and presence of common leukocyte antigen (CLA+). Cortical RE cells express a surface antigen, gp200-MR6, which plays a significant role of thymocyte differentiation. Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA-DR) molecule restriction. Thymic RE cells also produce numerous cytokines that are important in various stages of haematopoietic cell activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion, as well as the production of a number of interleukins and growth factors, and expression of receptors for all, by RE cells is an unique molecular biological phenomenon. Thymic neuroendocrine polypeptides are the source of self antigens presented by the MHC molecules to differentiating haematopoietic stem cells. On the level of individual RE cells, the numerous projections associated with a single cell, which engulf developing lymphocytes, nurturing and guiding them in their maturation, may differ in their hormone production and/or hormone receptor expression profile, thus allowing a single cell to be involved in distinct, separate steps of the T-cell and other haematopoietic cell maturation process. Thymic RE cells represent an important cellular and humoural network within the thymic microenvironment and are involved in the homeopathic regulation mechanisms of the multicellular organism. The intrathymic T-lymphocyte selection is a complex, multistep process, influenced by several functionally specialised RE cells and under immuno-neuroendocrine regulation control reflecting the dynamic changes of the mammalian organism. 相似文献
60.
The key elements of the optimization practice as applied to radiation protection are the monetary value of the averted person-sievert and the aversion coefficient. Determination of the monetary value of the unit averted person-sievert (as alpha(base)-parameter) in Hungary was presented in a previous paper. The estimation of this parameter was carried out by the willingness-to-pay (WTP) method associated with averted occupational exposure (at the NPP Paks/Hungary). The aversion coefficient predicts the importance of dose reduction based on the magnitude of the dose. The assessment of the aversion coefficient occurred also by means of the WTP method in the spring of 2000. Its value has been estimated on the basis of individual preferences concerning the distribution of individual exposure in nuclear safety. The results achieved by the WTP among the radiation specialists from the NPP Paks, Hungary, assessed a value for the aversion coefficient of 1.86 over the whole range of individual exposure levels. This value is a bit greater than the value obtained in France (1.7) and the higher coefficient expresses a higher priority to reduce the highest individual exposures. 相似文献