全文获取类型
收费全文 | 2644篇 |
免费 | 231篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 22篇 |
儿科学 | 64篇 |
妇产科学 | 62篇 |
基础医学 | 478篇 |
口腔科学 | 75篇 |
临床医学 | 271篇 |
内科学 | 541篇 |
皮肤病学 | 38篇 |
神经病学 | 211篇 |
特种医学 | 58篇 |
外科学 | 425篇 |
综合类 | 15篇 |
一般理论 | 1篇 |
预防医学 | 204篇 |
眼科学 | 20篇 |
药学 | 169篇 |
中国医学 | 1篇 |
肿瘤学 | 235篇 |
出版年
2023年 | 14篇 |
2022年 | 25篇 |
2021年 | 47篇 |
2020年 | 59篇 |
2019年 | 69篇 |
2018年 | 67篇 |
2017年 | 55篇 |
2016年 | 61篇 |
2015年 | 64篇 |
2014年 | 85篇 |
2013年 | 121篇 |
2012年 | 169篇 |
2011年 | 160篇 |
2010年 | 94篇 |
2009年 | 99篇 |
2008年 | 148篇 |
2007年 | 128篇 |
2006年 | 152篇 |
2005年 | 122篇 |
2004年 | 136篇 |
2003年 | 119篇 |
2002年 | 117篇 |
2001年 | 48篇 |
2000年 | 48篇 |
1999年 | 59篇 |
1998年 | 25篇 |
1997年 | 30篇 |
1996年 | 15篇 |
1995年 | 20篇 |
1994年 | 27篇 |
1993年 | 13篇 |
1992年 | 31篇 |
1991年 | 37篇 |
1990年 | 30篇 |
1989年 | 28篇 |
1988年 | 25篇 |
1987年 | 36篇 |
1986年 | 34篇 |
1985年 | 25篇 |
1984年 | 19篇 |
1983年 | 16篇 |
1982年 | 15篇 |
1979年 | 14篇 |
1977年 | 14篇 |
1976年 | 12篇 |
1974年 | 12篇 |
1970年 | 15篇 |
1969年 | 11篇 |
1967年 | 12篇 |
1966年 | 18篇 |
排序方式: 共有2890条查询结果,搜索用时 234 毫秒
21.
Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone 总被引:3,自引:0,他引:3
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)
Pirnay JP De Vos D Cochez C Bilocq F Pirson J Struelens M Duinslaeger L Cornelis P Zizi M Vanderkelen A 《Journal of clinical microbiology》2003,41(3):1192-1202
To study the epidemiology of Pseudomonas aeruginosa colonization in a 32-bed burn wound center (BWC), 321 clinical and 45 environmental P. aeruginosa isolates were collected by prospective surveillance culture over a 1-year period and analyzed by serotyping, drug susceptibility testing, and amplified fragment length polymorphism (AFLP) analysis. Among 441 patients treated at the center, 70 (16%) were colonized with P. aeruginosa, including 12 (17%) patients who were colonized on admission and 58 (83%) patients who acquired the organism during their stay. Of the 48 distinct AFLP genotypes found, 21 were found exclusively in the environment, 15 were isolated from individual patients only, and 12 were responsible for the colonization of 57 patients, of which 2 were also isolated from the environment, but secondary to patient carriage. Polyclonal P. aeruginosa colonization with strains of two to four genotypes, often with different antibiotic susceptibility patterns, was observed in 19 patients (27%). Two predominant genotypes were responsible for recurrent outbreaks and the colonization of 42 patients (60% of all colonized patients). The strain with one of those genotypes appeared to be endemic to the BWC and developed multidrug resistance (MDR) at the end of the study period, whereas the strain with the other genotype was antibiotic susceptible but resistant to silver sulfadiazine (SSD(r)). The MDR strain was found at a higher frequency in sputum samples than the SSD(r) strain, which showed a higher prevalence in burn wound samples, suggesting that anatomic habitat selection was associated with adaptive resistance to antimicrobial drugs. Repeated and thorough surveys of the hospital environment failed to detect a primary reservoir for any of those genotypes. Cross-acquisition, resulting from insufficient compliance with infection control measures, was the major route of colonization in our BWC. In addition to the AFLP pattern and serotype, analysis of the nucleotide sequences of three (lipo)protein genes (oprI, oprL, and oprD) and the pyoverdine type revealed that all predominant strains except the SSD(r) strain belonged to recently identified clonal complexes. These successful clones are widespread in nature and therefore predominate in the patient population, in whom variants accumulate drug resistance mechanisms that allow their transmission and persistence in the BWC. 相似文献
22.
Surface proteins of Streptococcus agalactiae and related proteins in other bacterial pathogens 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Clinical microbiology reviews》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Streptococcus agalactiae (group B Streptococcus) is the major cause of invasive bacterial disease, including meningitis, in the neonatal period. Although prophylactic measures have contributed to a substantial reduction in the number of infections, development of a vaccine remains an important goal. While much work in this field has focused on the S. agalactiae polysaccharide capsule, which is an important virulence factor that elicits protective immunity, surface proteins have received increasing attention as potential virulence factors and vaccine components. Here, we summarize current knowledge about S. agalactiae surface proteins, with emphasis on proteins that have been characterized immunochemically and/or elicit protective immunity in animal models. These surface proteins have been implicated in interactions with human epithelial cells, binding to extracellular matrix components, and/or evasion of host immunity. Of note, several S. agalactiae surface proteins are related to surface proteins identified in other bacterial pathogens, emphasizing the general interest of the S. agalactiae proteins. Because some S. agalactiae surface proteins elicit protective immunity, they hold promise as components in a vaccine based only on proteins or as carriers in polysaccharide conjugate vaccines. 相似文献
23.
In order to study the interface of calcium phosphate bioglass ceramics, cylinders of standard size were implanted in the tibiae of rabbits. The materials were evaluated by radiography, light microscopy and microradiography. Bioceramics with hydroxyapatite surface give rise to a closer contact with new bone than calcium phosphate glass ceramics. 相似文献
24.
Daphné Lehalle Roberto Colombo Michael O'Grady Bénédicte Héron Nada Houcinat Paul Kuentz Sebastien Moutton Arthur Sorlin Julien Thevenon Julian Delanne Sebastien Gay Caroline Racine Aurore Garde Frédéric Tran Mau‐Them Christophe Philippe Antonio Vitobello Sophie Nambot Frédéric Huet Yannis Duffourd François Feillet Christel Thauvin‐Robinet Sandrine Marlin Laurence Faivre 《American journal of medical genetics. Part A》2019,179(9):1756-1763
Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management. 相似文献
25.
In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis 总被引:5,自引:0,他引:5
Debrock S Vander Perre S Meuleman C Moerman P Hill JA D'Hooghe TM 《Human reproduction (Oxford, England)》2002,17(10):2523-2528
BACKGROUND: Endometrium can adhere to autologous peritoneum. This study was undertaken to determine the effect of the menstrual cycle phase and the presence and stage of endometriosis on in-vitro adhesion of endometrium onto autologous peritoneum. METHODS: This was performed in an academic medical research centre. Sixty-seven subfertile women with a visually normal pelvis (n = 18) and with biopsy-proven endometriosis (n = 49) were included. Endometrial and peritoneal biopsies were obtained at laparoscopy during menstrual, follicular and luteal phase. Endometrium was cultured in vitro with autologous peritoneum, followed by fixation, paraffin embedding, serial sectioning, hematoxylin-eosin and immunohistochemical staining. Endometrial-peritoneal adhesion was evaluated using light microscopy. RESULTS: Endometrial-peritoneal adhesion was observed in approximately 80% of the adhesion assays and was not affected by the phase of the cycle, or by the presence and stage of endometriosis. The continuity of the mesothelial layer was disrupted at the attachment sites. Epithelialization was observed along the edges to integrate the endometrial implant. After adhesion, histological changes were observed within and below the implant. CONCLUSIONS: Endometrium obtained during menstrual, follicular or luteal phase appears to have a similar potential to implant in vitro on autologous peritoneum, and this adhesion process is not affected by the stage of endometriosis. 相似文献
26.
Acute and long-term humoral immunity following active immunization of rabbits with inacctivated spores of various Encephalitozoon species 总被引:1,自引:0,他引:1
Sobottka I Iglauer F Schüler T Schmetz C Visvesvara GS Albrecht H Schwartz DA Pieniazek NJ Bartscht K Laufs R Schottelius J 《Parasitology research》2001,87(1):1-6
Microsporidia of the genus Encephalitozoon are increasingly being reported as a cause of severe, often disseminated infections, mainly in patients with acquired immunodeficiency
syndrome (AIDS). Immunological identification of each of the three recognized species (E. cuniculi, E. hellem, and E. intestinalis) requires the availability of specific immune sera. All sera available thus far have been generated by direct inoculation
of rabbits with virulent microsporidian spores. This study demonstrates for the first time that subcutaneous immunization
with inactivated spores of E. cuniculi, E. hellem, or E. intestinalis is capable of generating highly active rabbit hyperimmune sera to the homologous antigens, with maximal titers being 1:5,120,
1:1,280, and 1:2,560, respectively, as determined by the indirect immunofluorescence technique (IIF). Broad cross-reactivity
of the rabbit antisera with all heterologous Encephalitozoon antigens was determined by IIF and immunogold electron microscopy; however, only the E. hellem immune serum strongly cross-reacted with spores of Enterocytozoon bieneusi. During the 35-month follow-up period the antibody titers to the homologous antigens declined to 1:640, 1:160, and 1:320,
respectively. The observed decay curves for antibody titers against E. cuniculi, E. hellem, and E. intestinalis were fitted using mathematical modeling, resulting in a predicted duration for specific immune responses of about 7 years
on average. Knowledge of the magnitude and duration of specific immune responses is a prerequisite for further evaluation
of the concept of using inactivated microsporidian spores in the quest for vaccines against microsporidian infections.
Received: 10 April 2000 / Accepted: 18 July 2000 相似文献
27.
The biodegradation of different porous β-whitlockite materials are studied by in vivo experiments, radiographie follow-ups and light microscopy observations. The materials were implanted in rabbit tibiae for 16 mnth. Micropores play an important role in the biodegradation rate. The resorbing materials evoke an inflammation with plasma cells. The resorption starts in the medulla, and the phagocytosed particles are removed to the lymph nodes. Normal bone function can be restored after all the implant material is resulted. 相似文献
28.
29.
Strain-specific restriction of the antiphagocytic property of group A streptococcal M proteins
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Group A streptococcal M proteins are type-specific virulence factors that inhibit phagocytosis. We used two M proteins, M5 and Emm22, to analyze the influence of genetic background on the properties of M proteins. Mutant strains, engineered to lack these M proteins, were complemented with genes encoding the homologous or heterologous M protein, and the complemented strains were analyzed for phagocytosis resistance. Neither the M5 nor the Emm22 protein conferred phagocytosis resistance in the heterologous background, but they did do so in the homologous background. This was not due to lack of surface expression in the heterologous background. Moreover, the M5 and Emm22 proteins expressed in heterologous background appeared to have normal structure, since they were not affected in their ability to bind different human plasma proteins. In particular, M5 or Emm22 had normal ability to bind human complement inhibitors, a property that has been implicated in phagocytosis resistance. Results similar to those obtained with M5 and Emm22 were obtained in experiments with the M6 and Emm4 proteins. Together, these data suggest that the surface expression of M protein alone may not be sufficient to confer phagocytosis resistance and consequently that strain-specific factors other than M and Emm proteins may contribute to the ability of group A streptococci to resist phagocytosis. 相似文献
30.
Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Genes & development》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ataxia telangiectasia results from mutations of ATM and is characterized by severe neurodegeneration and defective responses to DNA damage. Inactivation of certain DNA repair genes such as DNA ligase IV results in massive neuronal apoptosis and embryonic lethality in the mouse, indicating the occurrence of endogenously formed DNA double-strand breaks during nervous system development. Here we report that Atm is required for apoptosis in all areas of the DNA ligase IV-deficient developing nervous system. However, Atm deficiency failed to rescue deficits in immune differentiation in DNA ligase IV-null mice. These data indicate that ATM responds to endogenous DNA lesions and functions during development to eliminate neural cells that have incurred genomic damage. Therefore, ATM could be important for preventing accumulation of DNA-damaged cells in the nervous system that might eventually lead to the neurodegeneration observed in ataxia telangiectasia. 相似文献