全文获取类型
收费全文 | 18689篇 |
免费 | 1167篇 |
国内免费 | 93篇 |
专业分类
耳鼻咽喉 | 297篇 |
儿科学 | 342篇 |
妇产科学 | 359篇 |
基础医学 | 2780篇 |
口腔科学 | 1784篇 |
临床医学 | 1491篇 |
内科学 | 4063篇 |
皮肤病学 | 423篇 |
神经病学 | 1278篇 |
特种医学 | 331篇 |
外科学 | 2098篇 |
综合类 | 49篇 |
一般理论 | 9篇 |
预防医学 | 2077篇 |
眼科学 | 229篇 |
药学 | 1423篇 |
中国医学 | 220篇 |
肿瘤学 | 696篇 |
出版年
2024年 | 30篇 |
2023年 | 212篇 |
2022年 | 416篇 |
2021年 | 777篇 |
2020年 | 502篇 |
2019年 | 665篇 |
2018年 | 817篇 |
2017年 | 540篇 |
2016年 | 606篇 |
2015年 | 674篇 |
2014年 | 899篇 |
2013年 | 1076篇 |
2012年 | 1561篇 |
2011年 | 1789篇 |
2010年 | 899篇 |
2009年 | 688篇 |
2008年 | 1122篇 |
2007年 | 1079篇 |
2006年 | 933篇 |
2005年 | 814篇 |
2004年 | 659篇 |
2003年 | 567篇 |
2002年 | 546篇 |
2001年 | 300篇 |
2000年 | 298篇 |
1999年 | 235篇 |
1998年 | 71篇 |
1997年 | 60篇 |
1996年 | 37篇 |
1995年 | 47篇 |
1994年 | 50篇 |
1993年 | 41篇 |
1992年 | 120篇 |
1991年 | 81篇 |
1990年 | 77篇 |
1989年 | 73篇 |
1988年 | 51篇 |
1987年 | 42篇 |
1986年 | 44篇 |
1985年 | 41篇 |
1984年 | 33篇 |
1983年 | 20篇 |
1982年 | 22篇 |
1980年 | 23篇 |
1979年 | 20篇 |
1978年 | 26篇 |
1973年 | 25篇 |
1971年 | 23篇 |
1970年 | 20篇 |
1969年 | 25篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
New microsatellite multiplex PCR for Candida albicans strain typing reveals microevolutionary changes 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sampaio P Gusmão L Correia A Alves C Rodrigues AG Pina-Vaz C Amorim A Pais C 《Journal of clinical microbiology》2005,43(8):3869-3876
Five new microsatellite loci were described and characterized for use as molecular markers for the identification and genetic differentiation of Candida albicans strains. Following the typing of 72 unrelated clinical isolates, the analysis revealed that they were all polymorphic, presenting from 5 to 30 alleles and 8 to 46 different genotypes. The discriminatory power obtained by combining the information generated by three microsatellites used in a multiplex PCR amplification strategy was 0.99, the highest ever reported. The multiplex PCR was later used to test a total of 114 C. albicans strains, including multiple isolates from the same patient collected from different body locations and along episodes of vulvovaginal infections. Three different scenarios for strain relatedness were identified: (i) different isolates that were revealed to be the same strain, (ii) isolates that were the same strain but that apparently underwent a process of microevolution, and (iii) isolates that corresponded to different strains. Analysis of the microevolutionary changes between isolates from recurrent infections indicated that the genotype alterations observed could be the result of events that lead to the loss of heterozygosity (LOH). In one case of recurrent infection, LOH was observed at the CAI locus, and this could have been related to exposure to fluconazole, since such strains were exposed to this antifungal during treatment. The analysis of microsatellites by a multiplex PCR strategy was found to be a highly efficient tool for the rapid and accurate differentiation of C. albicans strains and adequate for the identification of fine microevolutionary events that could be related to strain microevolution in response to environmental stress conditions. 相似文献
82.
Donnadieu E Jouvin MH Rana S Moffatt MF Mockford EH Cookson WO Kinet JP 《Immunity》2003,18(5):665-674
Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, F(c)epsilonRI. In humans, F(c)epsilonRI is expressed as a tetramer (alphabetagamma(2)) and a trimer (alphagamma(2)). The beta subunit is an amplifier of F(c)epsilonRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the F(c)epsilonRIbeta gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical beta, the other a novel truncated form, beta(T). In contrast to beta, beta(T) prevents F(c)epsilonRI surface expression by inhibiting alpha chain maturation. Moreover, beta(T) competes with beta to control F(c)epsilonRI surface expression in vitro. We propose that the relative abundance of the products of the beta gene may control the level of F(c)epsilonRI surface expression and thereby influence susceptibility to allergic diseases. 相似文献
83.
Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage. 总被引:3,自引:0,他引:3
V A Alves L C Gayotto T De Brito R T Santos A Wakamatsu M R Vianna E E Sakata 《Experimental and toxicologic pathology》1992,44(7):425-434
In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine. 相似文献
84.
Bareket Falk Ruth Burstein Isaack Ashkenazi Ofer Spilberg Jacob Alter Ester Zylber-Katz Ardon Rubinstein Nava Bashan Yair Shapiro 《European journal of applied physiology》1989,59(3):168-173
Summary The purpose of this study was to determine the effect of caffeine ingestion on physical performance after prolonged endurance
exercise. Twenty three trained male volunteers participated in a 40-km march and were divided into two groups, matched for
caffeine clearance rate and aerobic capacity. The experimental group ingested, prior to the march, a caffeinated drink at
a dose of 5 mg·kg−1 body mass and at the 3rd and 5th h of marching an additional drink at a dose of 2.5 mg·kg−1 body mass. The control group ingested a drink of equal volume at the same times. Upon termination of the march each subject
performed a cycle ergometer test at an intensity of 90% maximal oxygen consumption. Time to exhaustion and rate of perceived
exertion (RPE) were recorded. Blood samples were drawn predrink, at the 3rd and 5th h of marching and immediately after the
cycle ergometer test, and were analysed for caffeine, free fatty acids (FFA), lactate and glucose levels. Plasma FFA levels
increased during the march (p<0.05), with no significant difference between groups. Lactate levels increased in the experimental group (p<0.05), with no significant change in the control group. Glucose levels did not change significantly in either group. After
the cycle ergometer test, lactate levels were significantly higher in the experimental, as compared to the control group (3.77±0.33
vs 2.52±0.35 mmol·l−1, respectively). There was no significant difference between treatments in the time to exhaustion on the cycle ergometer,
but RPE was different (p<0.05). Under the conditions of this study, the results do not indicate caffeine ingestion as an ergogenic aid which will
postpone exhaustion following prolonged endurance exercise.
This work was presented, in part, at the Canadian Association of Sports Sciences Annual Meeting, October 1987, Lake Louise,
Alberta, Canada 相似文献
85.
Nunes S Sá-Leão R Carriço J Alves CR Mato R Avô AB Saldanha J Almeida JS Sanches IS de Lencastre H 《Journal of clinical microbiology》2005,43(3):1285-1293
Of the nasopharyngeal cultures recovered from 942 day care center (DCC) attendees in Lisbon, Portugal, 591 (62%) yielded Streptococcus pneumoniae during a surveillance performed in February and March of 1999. Forty percent of the isolates were resistant to one or more antimicrobial agents. In particular, 2% were penicillin resistant and 20% had intermediate penicillin resistance. Multidrug resistance to macrolides, lincosamides, and tetracycline was the most frequent antibiotype (17% of all isolates). Serotyping and molecular typing by pulsed-field gel electrophoresis were performed for 202 out of 237 drug-resistant pneumococci (DRPn). The most frequent serotypes were 6B (26%), 14 (22%), 19F (16%), 23F (10%), and nontypeable (12%). The majority (67%) of the DRPn strains were representatives of nine international clones included in the Pneumococcal Molecular Epidemiology Network; eight of them had been detected in previous studies. Fourteen novel clones were identified, corresponding to 26% of the DRPn strains. The remaining 7% of the strains were local clones detected in our previous studies. Comparison with studies conducted since 1996 in Portuguese DCCs identified several trends: (i) the rate of DRPn frequency has fluctuated between 40 and 50%; (ii) the serotypes most frequently recovered have remained the same; (iii) nontypeable strains appear to be increasing in frequency; and (iv) a clone of serotype 33F emerged in 1999. Together, our observations highlight that the nasopharynxes of children in DCCs are a melting pot of successful DRPn clones that are important to study and monitor if we aim to gain a better understanding on the epidemiology of this pathogen. 相似文献
86.
Presence of the cfxA gene in Bacteroides distasonis 总被引:1,自引:0,他引:1
Avelar KE Otsuki K Vicente AC Vieira JM de Paula GR Domingues RM Ferreira MC 《Research in microbiology》2003,154(5):369-374
In this study we investigated the presence of the cfxA gene (encoding a class A beta-lactamase) in 73 strains of the Bacteroides fragilis group belonging to the species B. distasonis (34), B. vulgatus (14), B. thetaiotaomicron (8), B. merdae (6), B. caccae (9) and B. ovatus (2) isolated from human intestinal microflora of healthy children and adults. Employing specific primers to the cfxA gene, a 312-bp amplified fragment was obtained in 2 strains of B. vulgatus and 9 strains, the majority from children, of B. distasonis. The expression of this enzyme was analysed by determining the MICs to cefoxitin and cefotaxime and values varied from 2 to >256 microg/ml of both cefoxitin and cefotaxime. Sequence analysis of the amplicons corresponding to the cfxA gene from B. distasonis and B. vulgatus revealed identical sequences between these isolates and high similarity with other beta-lactamase genes of anaerobes such as cfxA of B. vulgatus (99%) and cfxA2 of Prevotella intermedia (99%), both sequences of which deposited in Genbank under accession numbers U38243 and AF118110, respectively. However, a fragment obtained from a B. distasonis strain (EC17-4) showed a unique RFLP profile and 87% nucleotide similarity with cfxA and cfxA2 genes. These results seem to suggest a dissemination of these resistance determinants among Bacteroides species. 相似文献
87.
Ma Cruz García Rodríguez Eduardo Lpez Granados Antonio Ferreira Cerdn Gumersindo Fontn Casariego 《Human mutation》2001,18(1):84-84
Mutations in Bruton’s tyrosine kinase (BTK) gene result in X linked agammaglobulinemia (XLA). Using Single Strand Conformation Polymorphism (SSCP) followed by direct sequencing 21 mutations were found in 27 patients with an XLA phenotype from 21 unrelated families. We identified 13 novel and 8 known mutations: seven missense (R288W, R544G, P566S, K430E; K374N, L512P, R544S), 5 nonsense (Q196X, Y361X, L249X, Q612X, Q466X), 2 deletions of one nucleotide (A207fsX216, Q612fsX648), 2 deletion‐insertions (V219fsX227, K218fsX228), one insertion of two nucleotides (S572fsX587) and 4 point mutations in donor/acceptor splice sites (g.IVS1+1G>C, g.IVS6+5G>A, g.IVS10+1G>T, g.IVS13‐1GG>CT). Carrier detection was performed in 18 mothers. Only in one case the mutation was found to be de novo. Additionally, BTK mutations were not found in four patients without family history, but with XLA‐compatible phenotype. Hum Mutat 18:84, 2001. © 2001 Wiley‐Liss, Inc. 相似文献
88.
R. S. C. Araújo E. M. B. Guimarães M. F. C. Alves E. Sakurai L. T. Domingos F. C. R. Fioravante A. C. S. Machado 《European journal of clinical microbiology & infectious diseases》2006,25(6):397-400
In order to determine the prevalence and risk factors for Chlamydia trachomatis infection in adolescent females and young women in central Brazil, 296 subjects attending two public health services were evaluated. The overall prevalence of C. trachomatis infection, as determined using polymerase chain reaction, was 19.6% (95% confidence interval [CI], 15.3–24.7). In multivariate analysis, young age (odds ratio [OR]adjusted 2.32, 95%CI 1.1–4.8, p<0.05) and having 2–3 (ORadjusted 3.41, 95%CI 1.6–6.3, p<0.05) or ≥4 sexual partners in life (ORadjusted 3.10, 95%CI 1.1–6.3, p<0.05) were factors significantly associated with chlamydial infection. In conclusion, the prevalence of C. trachomatis infection was high in the studied population and risk factors were related to age and sexual behavior. 相似文献
89.
Suriano G Oliveira MJ Huntsman D Mateus AR Ferreira P Casares F Oliveira C Carneiro F Machado JC Mareel M Seruca R 《Human molecular genetics》2003,12(22):3007-3016
In Hereditary Diffuse Gastric Cancer syndrome, E-cadherin germline mutations of the missense type harbour significant functional consequences. In this study, we have characterised the effect of T340A, A617T, A634V and V832M E-cadherin germline missense mutations on cell morphology, motility and proliferation. Wild-type E-cadherin and A617T expressing cells have an epithelial-like morphology, with polarised cells migrating unidirectionally. T340A and A634V expressing cells, fibroblast-like, have a high motile phenotype. We show that this phenotype is dependent on an increased level of active RhoA. V832M expressing cells grow in piled-up structure of round cells, as an effect of the disturbance of the binding between alpha-catenin and beta-catenin. The destabilisation of the adhesion complex is shown to hamper the motile capabilities of these cells. We did not observe any effect of the E-cadherin mutations on cell proliferation. We show the existence of a genotype-phenotype correlation between different E-cadherin mutations and cell behaviour. However, we demonstrate that the ability of cells expressing the different E-cadherin mutations to invade is independent on their motile capabilities, providing evidence that motility is neither necessary nor sufficient for cells to invade. Our data give new insights into the understanding of the mechanisms linking invasion and E-cadherin mutations in diffuse gastric cancer. 相似文献
90.
Gontijo AM Marcondes JP Elias FN de Oliveira ML de Lima RO Salvadori DM de Camargo JL 《Environmental and molecular mutagenesis》2002,40(3):190-199
In order to determine if patients with a history of previous urothelial cell carcinoma (UCC) but with current normal urinary cytology have DNA damage in urothelial cells, the single-cell gel electrophoresis (comet) assay was conducted with cells obtained by urinary bladder washings from 44 patients (28 with a history of previous UCC). Increased DNA damage was observed in cytologically "normal" urothelial cells of patients with a history of UCC when compared with referents with no similar history and after correcting the data for smoking status and age (P < 0.018). Increased DNA damage also correlated with the highest tumor grade, irrespective of time or course of the disease after clinical intervention (Kendall tau correlation, 0.37, P = 0.016). Moreover, aneuploidy, as assessed by DNA content ratio (DCR; 75th/25th percentile of total DNA fluorescence of 50 comets/patient) was unaltered by smoking status, but increased with UCC grade: 1.39 +/- 0.12 (median +/- 95% confidence interval; referents); 1.43 +/- 0.11 (Grade I UCC; P = 0.264, against referents); 1.49 +/- 0.16 (Grade II UCC; P = 0.057); 1.57 +/- 0.16 (Grade III UCC; P = 0.003). Micronucleated urothelial cells (MNC) were also scored on Giemsa-stained routine cytological smears and were found not to correlate with DNA damage or DCR. MNC frequencies were higher for patients with a history of UCC and/or smoking than referents with neither history, but there was no statistical difference between groups. Taken together, these results suggest that the normal-appearing urothelium of patients resected for UCC still harbor genetically unstable cells. 相似文献