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61.
Eichler EE; Macpherson JN; Murray A; Jacobs PA; Chakravarti A; Nelson DL 《Human molecular genetics》1996,5(3):319-330
To understand the origins of the fragile X syndrome and factors
predisposing alleles to instability and hyperexpansion, we have compared
the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG
interspersion patterns of the FMR1 CGG repeat for 214 normal and 16
premutation chromosomes. Association testing between interspersion pattern
and haplotype reveals a highly significant (P < 0.002) non- random
distribution, indicating that all three markers are useful in phylogenetic
reconstruction of mutational change. Parsimony analysis of the FMR1 CGG
repeat substructure predicts that loss of AGG interruptions has occurred
independently on many haplotypes associated with the fragile X syndrome,
partially explaining the haplotype diversity of this disease. Among
haplotypes found in linkage disequilibrium with the fragile X mutation, two
different modes of mutation and predisposition to instability have been
identified. One pathway has involved the frequent and recurrent loss of AGG
interruptions from rare asymmetrical ancestral array structures.
Intergenerational transmission studies suggest that these predisposed
chromosomes progress relatively rapidly to the disease state. In contrast,
the second mutational pathway involves a single haplotype which has
maintained two AGG interruptions. Parsimony analysis of CGG repeat
substructure within this haplotype suggests that larger alleles have been
generated by gradual increments of CGG repeats distal to the most 3'
interruption. Pedigree analysis of the intergenerational stability of
alleles of this haplotype confirms a gradual progression toward instability
thresholds. As a result, a large reservoir of chromosomes carrying large
repeats on this haplotype exists. These chromosomes are predisposed to
disease. The present data support a model in which there are at least two
different mutational pathways predisposing alleles to instability and
hyperexpansion associated with the fragile X syndrome.
相似文献
62.
Study of antibody and T cell responses in rabbits immunized with synthetic human B cell epitope analogues of La (SSB) autoantigen 下载免费PDF全文
Yiannaki E Vlachoyiannopoulos PG Manoussakis MN Sakarellos C Sakarellos-Daitsiotis M Moutsopoulos HM Tzioufas AG 《Clinical and experimental immunology》2000,121(3):551-556
The aim of this study was to investigate the immunogenicity of four synthetic peptides, representing linear B cell epitopes of the human La/SSB autoantigen: 145-164 aa (p1), 289-308 aa (p2), 301-318 aa (p3) and 349-364 aa (p4), in rabbits. New Zealand White rabbits were immunized with each of the above peptides attached in four copies on tetrameric sequential oligopeptide carriers (SOC) in duplicate. Control immunizations were also performed (one rabbit each, immunized with Freud's complete adjuvant alone or with the SOC carrier alone). Animals were bled at regular intervals and sera were analysed for anti-La/SSB activity by ELISA assays using as antigen the various synthetic peptides, as well as the whole La/SSB protein. Four months after the last immunization, the animals were killed and peripheral blood mononuclear and spleen cells were co-cultured with either the peptides, the SOC carrier, or 27 peptides, covering the entire length of the human La/SSB molecule (23 amino acids long, overlapping by eight residues to each other). A specific, IgG, anti-peptide antibody response was detected, initially directed against the priming peptide, and subsequently expanded to the other La/SSB synthetic peptides. The antibody titres remained high, even 4 months after the last immunization. Sera from rabbits immunized with either p2 or p3 reacted also with the whole La/SSB protein, as was demonstrated by ELISA and immunoblot assays. No reactivities against either Ro60 or Ro52 autoantigen were found. Rabbit spleen cell reacted not only with the epitope used for the immunization but also with other La/SSB peptides. Immunization of rabbits with the major human La/SSB B cell antigenic determinants, linked to SOC carrier, induces strong and sustained antibody and T cell responses against multiple epitopes of the human La/SSB protein. Thus, La/SSB B cell linear epitopes are probably capable also of functioning as T cell epitopes, in this experimental animal. 相似文献
63.
Arici A; Oral E; Bahtiyar O; Engin O; Seli E; Jones EE 《Human reproduction (Oxford, England)》1997,12(6):1233-1239
Leukaemia inhibitory factor (LIF) is a 43 kDa glycoprotein with a
remarkable range of biological actions in different tissue systems. LIF
improves the rate of fertilization of mouse oocytes in vitro and up-
regulates aromatase enzyme. We postulated that LIF may be an important
modulator of ovarian function and may also improve embryo quality in
humans. Follicular fluid samples from patients undergoing in-vitro
fertilization (IVF) and embryo transfer (n = 123), from women undergoing
ovarian stimulation (n = 4) and from women undergoing laparoscopy for tubal
ligation during their follicular phase (n = 3) were used. Follicular fluid
LIF, oestradiol, and progesterone were measured and embryo quality was
assessed. Granulosa-lutein cells were cultured for 3 days in Ham's
F-12:Dulbecco's modified Eagle's medium (DMEM). Ovarian stromal cells,
isolated by enzymatic dispersion of ovarian tissue, were also cultured in
the same medium. Following experimental treatments, LIF mRNA and protein
concentrations were quantified. The concentration of LIF was 0.8 +/- 0.3
(mean +/- SEM) pg/ml in pre-human chorionic gonadotrophin (HCG) follicular
fluid samples and 13.0 +/- 1.1 pg/ml in post-HCG follicular fluid samples
(P < 0.05). LIF levels were undetectable in three follicular fluid
samples obtained during unstimulated follicular phase. There was a
correlation between follicular fluid LIF and follicular fluid oestradiol
concentrations (r = 0.36; P = 0.0001) and the number of grade I embryos (r
= 0.62; P = 0.01). LIF mRNA and the protein were expressed constitutively
but in low amounts in the ovarian stromal cell cultures. The concentrations
of LIF mRNA as well as protein were increased by interleukin (IL)-1alpha
and tumour necrosis factor alpha (TNF alpha) in a time- and
concentration-dependent manner. Purified granulosa-lutein cells expressed
low amounts of LIF mRNA and protein which were not significantly increased
by IL-1alpha or TNF alpha. Our findings suggest that HCG stimulates the
expression of LIF in follicular fluid. Both granulosa-lutein and ovarian
stromal cells express the LIF mRNA and produce the protein. Modulation of
LIF in these cells may play an important role in the physiology of
ovulation and early embryo development.
相似文献
64.
Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma 总被引:10,自引:0,他引:10
EE Matthews PD Curtis BI McLain LS Morris ML Turbitt 《Acta paediatrica (Oslo, Norway : 1992)》1999,88(8):841-843
The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV1) and symptoms) were measured 24 h after treatment initiation. FEV1 improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma. 相似文献
65.
66.
Detrano R; MacIntyre WJ; Salcedo EE; O'Donnell J; Underwood DA; Simpfendorfer C; Go RT; Jones H; Butters K; Leatherman J 《Radiology》1985,155(1):19-23
Forty-three patients who had undergone direct-contrast ventriculography were submitted to intravenous digital subtraction ventriculography and first-pass radionuclide ventriculography to compare the left ventricular ejection fractions obtained by each method. Ejection fractions were calculated by the area-length method from the direct contrast ventriculograms, by both area-length and videodensitometric methods from the digital subtraction ventriculograms, and by count densitometry from the radionuclide ventriculograms. Satisfactory correlations were found between values obtained by the late mask resubtracted videodensitometric method and the radionuclide method (r = 0.85) and by the digital ventriculographic area length method and direct-contrast method (r = 0.88). Videodensitometric methods may be an alternative way to estimate left ventricular ejection fractions accurately without reliance on geometric assumptions about the shape of the left ventricular cavity. 相似文献
67.
JA Low AB Froese RS Galbraith JT Smith EE Sauerbrei EJ Derrick 《Acta paediatrica (Oslo, Norway : 1992)》1993,82(5):433-437
Ninety-eight newborn infants, less than 34 weeks at birth, were studied to examine the relationship between newborn hypotension and hypoxemia and brain damage. Heart rate, blood pressure and oxygen tension were recorded continuously during the 96 h following delivery. Outcome measures included neuropathology in children who died, and motor and cognitive development at one year corrected age in children who survived. There were 22 children with a minor and 27 with a major abnormal outcome. There was a relationship between newborn hypotension, newborn hypoxemia and low birth weight, and a major abnormal outcome. The probability of a major abnormal outcome increased from 8% in newborns with no hypotension or hypoxemia, to 53% in children with both hypotension and hypoxemia. These findings support the contention that combinations of sustained newborn hypotension and hypoxemia are important factors in the development of brain damage, accounting for a major abnormal outcome. 相似文献
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