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1.
2.
Autoantibodies to the alpha/beta T-cell receptors in human immunodeficiency virus infection: dysregulation and mimicry.
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D F Lake S F Schluter E Wang R M Bernstein A B Edmundson J J Marchalonis 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(23):10849-10853
Autoimmune reactivity is a consequence of infection with human immunodeficiency virus (HIV). We studied serological cross-reactions of purified pooled IgG from sera of HIV-infected individuals by using nested sets of synthetic overlapping peptides duplicating the covalent structures of T-cell receptors (TCRs) and immunoglobulin light chains and report that two processes of autoantibody production occur. (i) IgG autoantibodies to putative regulatory variable domain CDR1 and FR3 epitopes (where CDR is complementarity-determining region and FR is framework region) are present in pooled IgG from HIV-infected individuals at levels 10-fold greater than that in pooled IgG from healthy humans. (ii) Anti-TCR autoimmunization involves antigenic mimicry between a conserved peptide stretch of the major neutralizing V3 loop determinant of HIV-1 gp120 and the conserved FR4 segment of the TCR V beta. Affinity-purified antibodies to the synthetic V3 loop peptide bound to a recombinant single-chain TCR and to a synthetic TCR joining segment peptide containing the FR4 sequence. Conversely, affinity-purified autoantibodies from pooled IgG from HIV-infected individuals to the TCR peptide bound the V3 loop peptide and a single-chain TCR. Inhibition studies indicated that the cross-reactive immunizing antigen was the V3 loop. These results bear upon the impact of HIV infection on immune regulation and on the selection of peptides for vaccine development. 相似文献
3.
BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic
lipid profile and an increased risk of ischaemic cardiovascular disease.
The associated hyperlipidaemia is reportedly ameliorated by erythropoietin
(Epo) therapy. According to a recent report, rats studied 3 weeks after 5/6
nephrectomy and fed a high- protein diet exhibited increased activities of
hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase
(Ch-7 alpha- H), despite normal corresponding mRNA values. DESIGN AND
METHODS: This study was designed to examine the effects of naturally
progressing CRF of longer duration as well as those of Epo therapy on gene
expressions of the key factors involved in hepatic cholesterol metabolism,
i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H. Sprague-Dawley rats
were randomized to the CRF group (5/6 nephrectomy), Epo-treated CRF group
(given Epo 150 U/kg/twice weekly) and sham-operated, placebo- treated
normal controls. They were allowed free access to regular rat chow and
studied 6 weeks after surgery. Liver mRNAs and protein mass or activities
of the above factors were studied. RESULTS: Plasma cholesterol
concentration was significantly increased in the CRF group (P < 0.001)
and was modestly lowered (P < 0.05) by Epo therapy. However, microsomal
cholesterol concentration and LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA as well
as HMG-CoAR activity, and Ch-7 alpha-H and LDLR protein mass measurements
were virtually identical in the three groups. Thus, hepatic LDLR, HMG-CoAR,
and Ch-7 alpha-H mRNA and protein measurements in rats with CRF were
similar to those of the normal control group representing an inappropriate
response to the associated hypercholesterolemia. Epo therapy led to partial
amelioration of CRF- associated hypercholesterolaemia with no discernible
effect on hepatic tissue expression of the above factors.
相似文献
4.
5.
Diana Cardenas MD PhD Gustavo Díaz RD MSc Jessika Cadavid ND MSC Fernando Lipovestky MD Marisa Canicoba RD Paola Sánchez MD Ludwig Álvarez ND Yan Duarte MD José Guillermo Gutiérrez Reyes MD Gilda Miranda de Noyola RD Claudia Maza RD Sergio Santana Porbén MD Charles Elleri Bermúdez MD Yawelida García RN Isabel Calvo RD Humberto Arenas MD 《JPEN. Journal of parenteral and enteral nutrition》2022,46(1):229-237
6.
Signal-, set- and movement-related activity in the human brain: an event-related fMRI study 总被引:9,自引:6,他引:3
Toni I Schluter ND Josephs O Friston K Passingham RE 《Cerebral cortex (New York, N.Y. : 1991)》1999,9(1):35-49
Electrophysiological studies on monkeys have been able to distinguish sensory and motor signals close in time by pseudorandomly delaying the cue that instructs the movement from the stimulus that triggers the movement. We have used a similar experimental design in functional magnetic resonance imaging (fMRI), scanning subjects while they performed a visuomotor conditional task with instructed delays. One of four shapes was presented briefly. Two shapes instructed the subjects to flex the index finger; the other two shapes coded the flexion of the middle finger. The subjects were told to perform the movement after a tone. We have exploited a novel use of event-related fMRI. By systematically varying the interval between the visual and acoustic stimuli, it has been possible to estimate the significance of the evoked haemodynamic response (EHR) to each of the stimuli, despite their temporal proximity in relation to the time constant of the EHR. Furthermore, by varying the phase between events and image acquisition, we have been able to achieve high temporal resolution while scanning the whole brain. We dissociated sensory and motor components of the sensorimotor transformations elicited by the task, and assessed sustained activity during the instructed delays. In calcarine and occipitotemporal cortex, the responses were exclusively associated with the visual instruction cues. In temporal auditory cortex and in primary motor cortex, they were exclusively associated with the auditory trigger stimulus. In ventral prefrontal cortex there were movement-related responses preceded by preparatory activity and by signal-related activity. Finally, responses associated with the instruction cue and with sustained activity during the delay period were observed in the dorsal premotor cortex and in the dorsal posterior parietal cortex. Where the association between a visual cue and the appropriate movement is arbitrary, the underlying visuomotor transformations are not achieved exclusively through frontoparietal interactions. Rather, these processes seem to rely on the ventral visual stream, the ventral prefrontal cortex and the anterior part of the dorsal premotor cortex. 相似文献
7.
Attenuation of the protein wasting associated with bed rest by branched-chain amino acids. 总被引:2,自引:0,他引:2
T P Stein M D Schluter M J Leskiw G Boden 《Nutrition (Burbank, Los Angeles County, Calif.)》1999,15(9):656-660
Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest. 相似文献
8.
Abstract: Haemoptysis in otherwise healthy children is an uncommon event. Two cases of massive haemoptysis, subsequently requiring lobectomy, are discussed. In each case, foreign vegetable matter was identified despite previously normal bronchoscopy and minimal changes on chest radiograph. 相似文献
9.
Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer 总被引:2,自引:0,他引:2
Davidson LA; Aymond CM; Jiang YH; Turner ND; Lupton JR; Chapkin RS 《Carcinogenesis》1998,19(2):253-257
We have developed a non-invasive method utilizing feces, containing
sloughed colonocytes, as a sensitive technique for detecting diagnostic
colonic biomarkers. In this study, we used the rat colon carcinogenesis
model to determine if changes in fecal protein kinase C (PKC) expression
have predictive value in monitoring the neoplastic process. Weanling rats
were injected with saline or azoxymethane (AOM) and 36 weeks later fecal
samples and mucosa were collected, poly A+ RNA isolated, and quantitative
RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and
zeta mRNA levels were altered by the presence of a tumor, with
tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII
expression as compared with animals without tumors. In addition,
AOM-injection increased mucosal PKC betaII mRNA expression compared with
saline controls. No effect of tumor incidence on mucosal PKC betaII
expression was observed. In contrast, fecal PKC zeta expression was
2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus
saline. Since tumor incidence exerts a reciprocal effect on fecal PKC
betaII and zeta mRNA expression, data were also expressed as the ratio
between PKC betaII and zeta. The isozyme ratio was strongly related to
tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25,
animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that
the expression of fecal PKC betaII and zeta may serve as a noninvasive
marker for development of colon tumors. A sensitive technique for the
detection of colon cancer is of importance since early diagnosis can
substantially reduce mortality.
相似文献
10.