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51.
C. M. Kahler L. E. Martin G. C. Shih M. M. Rahman R. W. Carlson D. S. Stephens 《Infection and immunity》1998,66(12):5939-5947
The molecular basis for the resistance of serogroup B Neisseria meningitidis to the bactericidal activity of normal human sera (NHS) was examined with a NHS-resistant, invasive serogroup B meningococcal isolate and genetically and structurally defined capsule-, lipooligosaccharide (LOS)-, and sialylation-altered mutants of the wild-type strain. Expression of the (α2→8)-linked polysialic acid serogroup B capsule was essential for meningococcal resistance to NHS. The very NHS-sensitive phenotype of acapsular mutants (99.9 to 100% killed in 10, 25, and 50% NHS) was not rescued by complete LOS sialylation or changes in LOS structure. However, expression of the capsule was necessary but not sufficient for a fully NHS-resistant phenotype. In an encapsulated background, loss of LOS sialylation by interrupting the α2,3 sialyltransferase gene, lst, increased sensitivity to 50% NHS. In contrast, replacement of the lacto-N-neotetraose α-chain (Galβ1-4GlcNAcβ1-3Galβ1-4Glc) with glucose extensions (GlcN) in a galE mutant resulted in a strain resistant to killing by 50% NHS at all time points. Encapsulated meningococci expressing a Hep2(GlcNAc)→KDO2→lipid A LOS without an α-chain demonstrated enhanced sensitivity to 50% NHS (98% killed at 30 min) mediated through the antibody-dependent classical complement pathway. Encapsulated LOS mutants expressing truncated Hep2→KDO2→lipid A and KDO2→lipid A structures were also sensitive to 50% NHS (98 to 100% killed at 30 min) but, unlike the wild-type strain and mutants with larger oligosaccharide structures, they were killed by hypogammaglobulinemic sera. These data indicate that encapsulation is essential but that the LOS structure contributes to the ability of serogroup B N. meningitidis to resist the bactericidal activity of NHS.Serogroup B Neisseria meningitidis (the meningococcus) is an obligate human pathogen and remains a leading cause of fulminant septicemia and meningitis. In addition to sporadic outbreaks, large epidemics of serogroup B meningococcal disease continue to occur in many parts of the world, including South America, the United States Pacific Northwest, Western Europe, and New Zealand (4, 22). After penetrating upper respiratory tract mucosal surfaces, N. meningitidis must survive and multiply in the bloodstream to cause sepsis, meningitis, and other manifestations of invasive meningococcal disease. A major mechanism inhibiting or preventing the multiplication of meningococci in the blood is the complement-mediated bactericidal activity of human sera (17, 39). The importance of this activity in the prevention of systemic meningococcal disease is reinforced by host factors that alter bactericidal activity and increase the risk for development of invasive disease. These factors include the absence of bactericidal antibodies against meningococci (17, 18, 45), deficiencies in the complement cascade (13), and the presence of blocking immunoglobulin A antibodies that inhibit the bactericidal activity of human sera (19). The bactericidal activity of human sera against meningococci is also used as a surrogate marker for assessing meningococcal vaccine efficacy.Meningococci have evolved mechanisms that protect them from the bactericidal activity of human sera. Invasive serogroup B meningococcal strains recovered from blood and cerebrospinal fluid often resist being killed by human sera (48). The molecular basis for resistance has been attributed to the expression by this organism of an (α2→8)-linked polysialic acid capsule and a short-chained lipooligosaccharide (LOS) with terminal sialic acid residues (23, 34, 35). Meningococci isolated from the bloodstream in invasive disease, in contrast to nasopharyngeal isolates, are heavily encapsulated (9) and express the L3,7,9 LOS immunotypes (28). These immunotypes have a lacto-N-neotetraose originating from HepI of the inner core, which may be terminally sialylated (34, 62). However, the experimental data defining the precise contributions of the capsule, LOS sialylation, and LOS structure to the ability of serogroup B meningococci to resist the bactericidal activity of human sera is conflicting (11, 15, 20, 21, 27, 37, 63–65).LOS epitopes are immunogenic in infants and children and induce protective bactericidal antibodies in convalescent sera (10, 12). These bactericidal LOS antibodies appear to be directed at conserved low-molecular-weight LOS epitopes (10, 12). LOS is also a component of new serogroup B outer membrane vesicle (OMV) vaccines and is proposed as a basis for other new meningococcal vaccines (1–3, 50). Although changes in the structure of LOS are known to influence the amount and epitopes of bactericidal and other functional antibodies elicited by OMV vaccines (2), the precise LOS structure(s) to include in these and other LOS-containing meningococcal vaccines is uncertain.To help understand the basis for meningococcal survival following mucosal invasion and to facilitate development of meningococcal vaccines which may contain LOS, we created a series of genetically and structurally defined capsule-, sialylation-, and LOS-altered mutants of the serogroup B meningococcal strain NMB. We used these mutants to study the contributions of the capsule, LOS sialylation, and changes in LOS structure to meningococcal resistance to the bactericidal activity of normal human sera (NHS). 相似文献
52.
Hepatitis B virus propagated in a rat hepatoma cell line is infectious in a primate model 总被引:1,自引:0,他引:1
The human hepatitis B virus (HBV) produced by a rat hepatoma cell line through transfection with HBV DNA is infectious in the human primate model--chimpanzee. Since hepadnaviruses are known to have an extremely narrow host range, our results support the idea that the host species barrier of HBV infection resides on the penetration/adsorption step rather than any postpenetration intracellular event during the virus life cycle. 相似文献
53.
Albert Z. Kapikian Anthony R. Kalica J.Wai-Kuo Shih W.Lee Cline Thomas S. Thornhill Richard G. Wyatt Robert M. Chanock Hyun Wha Kim John L. Gerin 《Virology》1976,70(2):564-569
The buoyant density in cesium chloride of the human reoviruslike (HRVL) agent of infantile gastroenteritis was studied utilizing electron microscopy and complement fixation (CF) for the detection of reoviruslike particles in fractions of the density gradient. Three virus positive stool filtrates were studied. “Full” reoviruslike particles had a density of 1.35–1.37 g/cm3, whereas “empty” particles had a density of 1.29 g/cm3. Peak CF activity coincided with the peak fraction of both the “full” and “empty” reoviruslike particles. In addition, by differential centrifugation, CF activity was also associated with the virion and not a “soluble” antigen. 相似文献
54.
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献
55.
Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection 总被引:1,自引:17,他引:1
Van Opstal D; Los FJ; Ramlakhan S; Van Hemel JO; Van Den Ouweland AM; Brandenburg H; Pieters MH; Verhoeff A; Vermeer MC; Dhont M; In't Veld PA 《Human reproduction (Oxford, England)》1997,12(4):682-686
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic
sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome
aberrations including two cases of 47,XXY, four cases involving a 45,X cell
line and three autosomal trisomies. Molecular analysis of the parental
origin of the deleted or supernumerary chromosome was performed by using
polymorphic microsatellite markers. Six cases involving a sex chromosome
abnormality were found to be of paternal origin while the two trisomic
cases that could be analysed were of maternal origin. Two cases involved
the same infertile couple who had two consecutive ICSI pregnancies
terminated because of a chromosome abnormality. The replaced embryos in
both cases originated from a single batch of ICSI fertilized oocytes of
which part was used to initiate the first pregnancy and part was
cryopreserved and used to initiate the second pregnancy.
相似文献
56.
Billette J; Janse MJ; van Capelle FJ; Anderson RH; Touboul P; Durrer D 《The American journal of physiology》1976,231(4):1129-1139
57.
Mucous membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the basement membrane zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy. 相似文献
58.
Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan 总被引:6,自引:0,他引:6
Lu CY Lee CY Kao CL Shao WY Lee PI Twu SJ Yeh CC Lin SC Shih WY Wu SI Huang LM 《Journal of medical virology》2002,67(2):217-223
In 1998, an epidemic of hand-foot-and-mouth disease and herpangina caused by enterovirus 71 occurred in Taiwan, leaving many fatalities and severely handicapped survivors in its wake. The reasons this rather common pathogen would cause such a large-scale epidemic remain unknown. A seroepidemiological survey to elucidate the epidemiological characteristics of this outbreak, including its incidence and case-fatality rates was undertaken. Microneutralization tests for antibodies against enterovirus 71 were used to screen four collections of serum samples: 1) 202 specimens taken from individuals > or = 4 years old in 1994; 2) 245 specimens collected from individuals of all ages in 1997; 3) 1,258 specimens collected from individuals of all ages in 1999; and 4) sera samples from a birth cohort of 81 children who had yearly blood samples taken from 1988-98. After the maternal antibody had declined, the seropositive rates began to increase with age. Approximately half of all children aged 6 years or older were enterovirus 71 seropositive. Significantly higher seropositive rates were noted in 1999 than in 1997, in children aged 0.5-3 years. The incidence of enterovirus 71 infection during the epidemic was estimated to be 13-22%, with the higher rates in younger children. The case-fatality rate was highest (96.96 per 100,000) in infants aged 6-11 months, and declined in older children. The results showed that enterovirus 71 is endemic in Taiwan. The apparent lack of large-scale enterovirus 71 activity in the 3 years before 1998 might have been the prelude to the epidemic's appearance in 1998, and might suggest that enterovirus 71 infection will reappear every few years. The lack of a protective antibody in younger children may account for the high incidence and case-fatality rate in this age group. 相似文献
59.
Bruce Ho PhD Woodrew Chao Reza Sadri Lu Huang Ricky Taira Henry Shih 《Journal of digital imaging》1995,8(4):180-190
A key advantage in the conversion from film-based to digital radiology is the possibility of a long-term on line electronic archival of patient studies. The popular approach based on optical disk jukeboxes for the long-term archive and magnetic disk storage for data caching is not economically attractive because of the cost of both the jukebox and the medium. Strategies for extending the archival system design with a tape jukebox have been studied. The proposed strategy calls for the use of high-ratio lossy compression together with low-cost tape storage to make long-term on line archiving more affordable. An intelligent prefetching algorithm based on hospital information system and radiologic information system triggers, which in turn are augmented by manual case preparation, can effectively overcome the longer latency of ad hoc retrievals. This longer latency is caused by both system-level bottlenecks and the sequential access constraint of the tape drive. Strategies for image clustering and tape allocation by patient classification also enhance retrieval efficiency. This archival design using image compression, prefetching, and clustering could be implemented in many of the existing teleradiology and picture archiving and communication systems. 相似文献
60.
Hsin-I Shih Hsin-Chun Lee Nan-Yao Lee Chia-Ming Chang Chi-Jung Wu Li-Rong Wang Nai-Ying Ko Wen-Chien Ko 《Journal of microbiology, immunology, and infection》2005,38(5):350-357
Antimicrobial resistance of isolates and risk factors for mortality were retrospectively investigated in 71 adult patients with Serratia marcescens bacteremia. During the 4-year study period, 78 clinically significant episodes of S. marcescens bacteremia occurred in 71 patients. The mean age of the patients was 65 years (range, 25-86 years) with a male predominance (45 patients, 63%). Most of the bacteremic episodes were nosocomial (78%), and 34% were polymicrobial. The overall mortality rate within 2 weeks after the onset of bacteremia was 41%. The presence of malignancy and critical illness at initial presentation were independent risk factors for mortality. By disk susceptibility test, 72 isolates were resistant to cefotaxime (92%) but susceptible to ceftazidime (99%). All isolates were susceptible to meropenem. Among the 47 patients with monomicrobial S. marcescens bacteremia, the mortality rate within 5 days of onset in patients receiving appropriate empirical antimicrobial therapy was lower than that in patients receiving inappropriate therapy although this difference was not significant (14% vs 28%, p = 0.27). Among the patients with cefotaxime-resistant but ceftazidime-susceptible S. marcescens bacteremia treated with ceftazidime, 6 of 7 patients (86%) survived for more than 2 weeks, suggesting the potential effectiveness of ceftazidime in the treatment of cefotaxime-resistant Serratia infections. Further clinical studies are required to delineate the clinical role of ceftazidime therapy for infections caused by S. marcescens with this resistant phenotype. 相似文献