全文获取类型
收费全文 | 13163篇 |
免费 | 948篇 |
国内免费 | 54篇 |
专业分类
耳鼻咽喉 | 157篇 |
儿科学 | 365篇 |
妇产科学 | 178篇 |
基础医学 | 1608篇 |
口腔科学 | 283篇 |
临床医学 | 1530篇 |
内科学 | 2953篇 |
皮肤病学 | 228篇 |
神经病学 | 1258篇 |
特种医学 | 631篇 |
外科学 | 2073篇 |
综合类 | 127篇 |
一般理论 | 5篇 |
预防医学 | 933篇 |
眼科学 | 334篇 |
药学 | 750篇 |
中国医学 | 15篇 |
肿瘤学 | 737篇 |
出版年
2023年 | 82篇 |
2022年 | 148篇 |
2021年 | 362篇 |
2020年 | 202篇 |
2019年 | 322篇 |
2018年 | 389篇 |
2017年 | 252篇 |
2016年 | 324篇 |
2015年 | 399篇 |
2014年 | 475篇 |
2013年 | 589篇 |
2012年 | 999篇 |
2011年 | 970篇 |
2010年 | 572篇 |
2009年 | 470篇 |
2008年 | 856篇 |
2007年 | 837篇 |
2006年 | 799篇 |
2005年 | 736篇 |
2004年 | 590篇 |
2003年 | 575篇 |
2002年 | 468篇 |
2001年 | 179篇 |
2000年 | 158篇 |
1999年 | 201篇 |
1998年 | 113篇 |
1997年 | 110篇 |
1996年 | 79篇 |
1995年 | 69篇 |
1994年 | 66篇 |
1993年 | 49篇 |
1992年 | 97篇 |
1991年 | 106篇 |
1990年 | 94篇 |
1989年 | 104篇 |
1988年 | 90篇 |
1987年 | 88篇 |
1986年 | 79篇 |
1985年 | 100篇 |
1984年 | 86篇 |
1983年 | 55篇 |
1982年 | 59篇 |
1981年 | 47篇 |
1980年 | 60篇 |
1979年 | 75篇 |
1978年 | 52篇 |
1976年 | 40篇 |
1975年 | 39篇 |
1972年 | 38篇 |
1971年 | 38篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
71.
Role of the Salmonella pathogenicity island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice 下载免费PDF全文
Hapfelmeier S Ehrbar K Stecher B Barthel M Kremer M Hardt WD 《Infection and immunity》2004,72(2):795-809
Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium) induces enterocolitis in humans and cattle. The mechanisms of enteric salmonellosis have been studied most extensively in calf infection models. The previous studies established that effector protein translocation into host cells via the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (TTSS) is of central importance in serovar Typhimurium enterocolitis. We recently found that orally streptomycin-pretreated mice provide an alternative model for serovar Typhimurium colitis. In this model the SPI-1 TTSS also plays a key role in the elicitation of intestinal inflammation. However, whether intestinal inflammation in calves and intestinal inflammation in streptomycin-pretreated mice are induced by the same SPI-1 effector proteins is still unclear. Therefore, we analyzed the role of the SPI-1 effector proteins SopB/SigD, SopE, SopE2, and SipA/SspA in elicitation of intestinal inflammation in the murine model. We found that sipA, sopE, and, to a lesser degree, sopE2 contribute to murine colitis, but we could not assign an inflammation phenotype to sopB. These findings are in line with previous studies performed with orally infected calves. Extending these observations, we demonstrated that in addition to SipA, SopE and SopE2 can induce intestinal inflammation independent of each other and in the absence of SopB. In conclusion, our data corroborate the finding that streptomycin-pretreated mice provide a useful model for studying the molecular mechanisms of serovar Typhimurium colitis and are an important starting point for analysis of the molecular events triggered by SopE, SopE2, and SipA in vivo. 相似文献
72.
Efficiency of Protection of Guinea Pigs against Infection with Bacillus anthracis Spores by Passive Immunization 总被引:7,自引:0,他引:7
David Kobiler Yehoshua Gozes Hagai Rosenberg Dino Marcus Shaul Reuveny Zeev Altboum 《Infection and immunity》2002,70(2):544-550
The efficacy of passive immunization as a postexposure prophylactic measure for treatment of guinea pigs intranasally infected with Bacillus anthracis spores was evaluated. Antisera directed either against the lethal toxin components (PA or LF) or against a toxinogenic strain (Sterne) were used for this evaluation. All antisera exhibited high enzyme-linked immunosorbent assay titers against the corresponding antigens, high titers of neutralization of cytotoxicity activity in an in vitro mouse macrophages cell line (J774A.1), as well as in vivo neutralization of toxicity when administered either directly to Fisher rats prior to challenge with the lethal toxin or after incubation with the lethal toxin. In these tests, anti-LF antiserum exhibited the highest neutralization efficiency, followed by anti-Sterne and anti-PA. The time dependence and antibody dose necessary for conferring postexposure protection by the various antibodies of guinea pigs infected with 25 50% lethal doses of Vollum spores was examined. Rabbit anti-PA serum was found to be the most effective. Intraperitoneal injections of anti-PA serum given 24 h postinfection protected 90% of the infected animals, whereas anti-Sterne and anti-LF were less effective. These results further emphasizes the importance of anti-PA antibodies in conferring protection against B. anthracis infection and demonstrated the ability of such antibodies to be effectively applied as an efficient postexposure treatment against anthrax disease. 相似文献
73.
Ion-exchange chromatography and gel filtration have been reported to yield partial separation of mycobacterial antigens. These procedures were used in combination with isoelectric focusing in an attempt to purify antigens of Mycobacterium tuberculosis strain H37Ra. The fractionating action of isoelectric focusing is dependent upon differences in the isoelectric points of the proteins to be separated. Culture filtrate of M. tuberculosis H37Ra was chromatographed on Sephadex G-200. This resulted in two widely separated peaks. The first peak, presumably containing high-molecular-weight substances, was then fractionated on a diethylaminoethyl Sephadex anion-exchange column. Three peaks were collected, and each was subjected to isoelectric focusing. Each peak was further separated into two or more fractions. The serological reactivity of each fraction was determined by immunodiffusion and immunoelectrophoresis. Sensitized guinea pigs were also skin-tested with the fractions. Two of the fractions contained only a single precipitinogen. One fraction contained two precipitinogens. A fourth fraction contained three precipitinogens and was also the only fraction to display sensitin activity. Four of the fractions were inactive either as precipitinogens or sensitins. The results suggest that the methods described are useful for the separation of mycobacterial antigens. 相似文献
74.
Perkins KA Levine M Marcus M Shiffman S D'Amico D Miller A Keins A Ashcom J Broge M 《Journal of consulting and clinical psychology》2000,68(1):176-180
Because negative mood is a characteristic of both tobacco withdrawal and menstrual discomfort, withdrawal may vary by menstrual cycle phase. Tobacco withdrawal, mood, and menstrual discomfort were assessed in premenopausal women who quit smoking during either the follicular (Days 1-14 postmenstrual onset; n = 41) or luteal (Day 15 or longer postmenstrual onset; n = 37) phase of the menstrual cycle and maintained biochemically verified smoking abstinence during the postquit week. Women quitting during the luteal phase reported significantly greater increases in tobacco withdrawal and self-reported depressive symptoms than women quitting during the follicular phase. These results indicate that selecting a quit-smoking day early in the follicular phase may attenuate withdrawal and negative affect in premenopausal female smokers. 相似文献
75.
Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system. 下载免费PDF全文
R Eren I Lubin D Terkieltaub O Ben-Moshe A Zauberman R Uhlmann T Tzahor S Moss E Ilan D Shouval E Galun N Daudi H Marcus Y Reisner S Dagan 《Immunology》1998,93(2):154-161
An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested. 相似文献
76.
X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions 总被引:5,自引:0,他引:5
Huber Irene; Bitner-Gllndzicz Maria; de Kok Yvette J.M.; van der Maarel Silvere M.; Ishikawa-Brush Yumiko; Monaco Anthony P.; Robinson David; Malcolm Susan; Pembrey Marcus E.; Brunner Han G.; Cremers Frans P.M.; Ropers Hans-Hilger 《Human molecular genetics》1994,3(7):1151-1154
We have found that the microsatellite marker AFM207zg5 (DXS995)maps to all previously described deletions which are associatedwith X-linked mixed deafness (DFN3) with or without choroideremiaand mental retardation. Employing this marker and pHU16 (DXS26)we have identified two partially overlapping yeast artificialchromosome clones which were used to construct a complete 850kb cosmid contig. Cosmids from this contig have been testedby Southern blot analysis on DNA from 16 unrelated males withX-linked deafness. Two novel microdeletions were detected inpatients which exhibit the characteristic DFN3 phenotype. Bothdeletions are completely contained within one of the known DFN3-deletions,but one of them does not overlap with two previously describeddeletions in patients with contiguous gene syndromes consistingof DFN3, chorolderemia, and mental retardation. Assuming thatonly a single gene is involved, this suggests that the DFN3gene spans a chromosomal region of at least 400 kb. 相似文献
77.
The heart in hypertension. 总被引:10,自引:0,他引:10
78.
Marie-Laure Muiras Marcus Müller François Schächter A. Bürkle 《Journal of molecular medicine (Berlin, Germany)》1998,76(5):346-354
Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins which is catalyzed by poly(ADP-ribose) polymerase
and represents an immediate response of eukaryotic cells to oxidative and other types of DNA damage. Previously a strong correlation
had been detected between maximal poly(ADP-ribose) polymerase activity in permeabilized mononuclear leukocytes of various
mammalian species and species-specific life span. To study a possible relation between longevity and poly(ADP-ribosyl)ation
in humans we measured maximal oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized, Epstein-Barr
virus transformed lymphoblastoid cell lines from a French population of 49 centenarians and 51 controls aged 20–70 years.
Maximal enzyme activity was significantly higher in centenarians than in controls [median of controls: 9035 cpm/106 cells (lower quartile: 6156; upper quartile: 11,410); median of centenarians: 10,380 cpm/106 cells (lower quartile: 7994; upper quartile: 12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24 centenarians, cellular poly(ADP-ribose) polymerase content was determined by quantitative
western blotting, thus allowing the calculation of specific enzyme activity. The latter was significantly higher in centenarians
(P=0.006), the median value for centenarians being about 1.6-fold that of controls. Specific poly(ADP-ribose) polymerase activity
was a more powerful parameter for differentiating between centenarians and controls than enzyme activity relative to cell
number. In addition, in a genetic association study we analyzed 437 DNA samples (239 centenarians and 198 controls) by PCR
amplification of a polymorphic dinucleotide repeat located in the promoter region of the poly(ADP-ribose) polymerase gene
in an attempt to detect an association between this polymorphic marker and variability of enzyme activity or human longevity.
However, this genetic analysis revealed no significant enrichment of any of the alleles or genotypes identified among centenarians
or controls, but its power was limited by the relatively weak hetero-zygosity of this polymorphic marker in our population
(51%). Viewed together with previous results on poly(ADP-ribose) polymerase activity in various mammalian species, the present
data provide further evidence for the notion that longevity is associated with a high poly(ADP-ribosyl)ation capacity.
Received: 5 September 1997 / Accepted: 10 November 1997 相似文献
79.
Synergistic interaction of topographic features in the production of bone-like nodules on Ti surfaces by rat osteoblasts 总被引:4,自引:0,他引:4
The objective of this study was to study the responses of osteoblast-like cells to rough Titanium (Ti)-coated epoxy surfaces of differing topographic complexity. Four topographies were studied: polished (PO), coarse-blasted (CB), acid-etched (AE) and coarse-blasted+acid-etched (SLA). Rat osteoblasts were cultured on these surfaces and their morphology, thickness as well as the number and size of bone-like nodules measured. To determine cell shape and cell thickness, fluorescein-5-thiosemicarbazide was used to stain the cell components including the cell membrane, the stained cells were optically sectioned using epifluorescent microscopy and the optical sections were computationally reconstructed to obtain three-dimensional images in which cell volume and cell thickness could be determined. Similarly optical sections of bone-like nodules labeled with tetracycline were also reconstructed to determine their size. The different surface topographies were found to alter the thickness and morphology of osteoblasts cultured on these surfaces. Osteoblasts produced significantly more and larger nodules on SLA compared to other surfaces. Nevertheless and perhaps surprisingly, given the evidence in various cell populations that cell shape can affect cell differentiation, cell thickness was not directly correlated with an increase in bone-like nodule formation. Data were analyzed by factorial analysis of variance. In this way the primary effect of each surface treatment ( i.e. blasting and acid etching) could be assessed as well as their interaction. Both the acid etching and blasting processes significantly affected the number and size of bone-like nodules cultured on Ti surfaces. Moreover there were significant interaction effects indicating that surface topographic features can act synergistically to enhance bone formation. This result suggests that a useful approach to the optimization of surfaces for bone production could involve systematic investigation of combinations of processes each of which produces distinct surface topographical features. 相似文献
80.
Long-term safety study of levalbuterol administered via metered-dose inhaler in patients with asthma. 总被引:1,自引:0,他引:1
Daniel L Hamilos Anthony D'Urzo Robin J Levy Michael Marcus Kenneth Tripp Merdad Parsey Rudolf A Baumgartner William K McVicar 《Annals of allergy, asthma & immunology》2007,99(6):540-548
BACKGROUND: Previous studies have raised concerns regarding the safety of regular use of beta2-agonists for treating asthma. Few studies have explored the safety of at least 1 year of use of racemic albuterol, and none have examined long-term dosing of levalbuterol. OBJECTIVE: To examine the long-term safety of levalbuterol hydrofluoroalkane (HFA) vs racemic albuterol HFA administered via metered-dose inhaler (MDI) in patients with stable asthma. METHODS: Patients with mild to moderate asthma (mean forced expiratory volume in 1 second [FEVI], 68.3% of predicted) 12 years or older participated in a multicenter, parallel-group, open-label study. Patients were randomized to levalbuterol HFA MDI (90 microg; 2 actuations of 45 microg; n = 496) or racemic albuterol HFA MDI (180 microg; 2 actuations of 90 microg; n = 250) for 52 weeks of 4 times daily dosing. The primary end point was the incidence of postrandomization adverse events. Asthma exacerbations and pulmonary parameters were also assessed. RESULTS: The overall incidence of adverse events was similar for levalbuterol (72.0%) and racemic albuterol (76.8%). Rates of beta-mediated adverse events, serious adverse events, and discontinuations because of adverse events were low (<15%) and were comparable between groups. Rates of asthma adverse events for levalbuterol and racemic albuterol were 18.3% and 19.6%, respectively. Mean percentage of predicted FEV1 improved after dosing and was stable for both groups. CONCLUSION: In this trial, up to 52 weeks of regular use of levalbuterol HFA MDI or racemic albuterol HFA MDI was well tolerated, and no deterioration of lung function was detected during the study period. 相似文献