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31.
Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas 总被引:2,自引:0,他引:2 下载免费PDF全文
Magro G Perissinotto D Schiappacassi M Goletz S Otto A Müller EC Bisceglia M Brown G Ellis T Grasso S Colombatti A Perris R 《The American journal of pathology》2003,163(1):183-196
Previous studies have suggested that surface components of papillary thyroid carcinoma (PTC) cells may be aberrantly glycanated, but the precise nature of these molecules has not been unveiled nor documented to be of clinical relevance. A monoclonal antibody was raised against a unique keratan sulfate (KS) determinant and used to differentially screen benign and malignant thyroid tissue for the expression of components carrying these moieties. In a total of 349 cases of benign and malignant thyroid lesions, 100% of the 115 PTC cases examined (including various histological subtypes) were found to contain KS-bearing molecules, whereas these were virtually absent from benign tissues and other thyroid tumors, with the exception of 21% of the follicular carcinoma cases analyzed. A composite immunoaffinity chromatography, immunochemistry, and mass spectrometric approach revealed that the PTC-specific KS-bearing macromolecules were unique glycoforms of thyroglobulin and transferrin. Combined, reciprocal immunoprecipitation and Western blotting further indicated that the former glycoform predominated and that most of the transferrin produced by PTC was glycanated with KS moieties. Fluorescent keratanase II-based fingerprinting of the KS moieties bound to these isoforms further demonstrated several PTC-specific peculiarities: 1) that a considerable portion of the moieties was covalently attached via a novel core protein linkage structure; 2) they had an unusual extended average length; 3) an unusual relative ratio of highly sulfated disaccharides terminating with alpha (2-3)-linked N-acetylneuraminic acid capping residues; and 4) a novel unidentified oligosaccharide moiety at the nonreducing terminus. Comparative analysis of the relative distribution of transferrin in benign versus PTC tissues highlighted a marked malignancy-associated abundance of the molecule, with a >75% frequency in expression in PTC. These findings demonstrate that PTC cells synthesize unique post-translationally modified thyroglobulin and transferrin variants in situ that may be directly exploitable for diagnosis, through histological and noninvasive cytological procedures; for devising novel strategies for antibody-guided imaging of this tumor in vivo; and for postsurgery follow-up of PTC patients. 相似文献
32.
Ghrelin is a novel peptide that stimulates the release of growth hormone from the pituitary and is involved in hypothalamic feeding regulation. A pre-embedding immunostaining technique was used to study the ultrastructure and synaptic relationships of ghrelin-containing neurons in the rat arcuate nucleus (ARC). Ghrelin-like immunoreactive (ghrelin-LI) neurons were found in the ARC, and were especially abundant in its ventral part. At the electron microscopic level, ghrelin-LI neurons received afferent synapses from many unknown axon terminals. Ghrelin-LI products in the immunoreactive cell bodies, processes, and axon terminals were detected mainly in dense granular vesicles about 110 nm in diameter. Ghrelin-LI presynaptic axon terminals often made synapses with unknown immunonegative neurons. These results suggest that ghrelin acts to regulate food intake through synaptic connections in hypothalamic neuronal networks. 相似文献
33.
Infection of wild marmosets (Saguinus mystax) with strains of parainfluenza virus types 1 and 3 resulted in acute respiratory infection. Virus replication in the upper respiratory tract was of a degree similar to that seen in children acutely infected with parainfluenza viruses. Serum antibody developed with both virus types; however, local secretory antibody was not detectable. The infection was transmissible to susceptible animals up to 3 days inoculation of the primary animal. 相似文献
34.
Dr. med. Gerhard Mall Helmut Reinhard Doris Stopp Johannes Albrecht Rossner 《Virchows Archiv : an international journal of pathology》1980,385(2):169-180
Summary Male Wistar rats were treated with high cortisol doses for 1 week. The dose administered daily was 15 mg per animal in group 1 (7 animals) and 30 mg in group 2 (7 animals). 7 rats served as control group. After cortisol treatment the body weights decreased due to skeletal muscle catabolism and the heart weights increased. Morphometric analysis of the left ventricular posterior papillary muscles gave evidence that the increased heart weights resulted from an increased number of mitochondria and an increased volume of the cytoplasm, whereas the myofibrillar mass was not affected. The surface area of inner mitochondrial membranes (+cristae mitochondriales) per myofibrillar unit volume increased from 15.7 2/3 to 21.3 2/3 in group 1 and 21.4 2/3 in group 2. Ultrastructural changes indicating myocardial cell damage were absent. Similar quantitative results have been reported to occur in the early phase of cardiac overload. For elucidating the hemodynamic effects of glucocorticoid a second experiment was performed: 7 Wistar rats were treated with cortisol in the same way as group 1, 7 others of the same body weight served as control. The systolic arterial pressure was significantly elevated in the cortisol group. Though myocardial tissue is known to be able to accumulate large quantities of glucocorticoids our results indicate that the application of high cortisol doses for a short time does not produce myocardial cell damage and does not suppress the myocardial adaption to the glucocorticoid-induced hypertension, i.e. hypertrophy. On the contrary, it seems to be possible that the adaption process is itself facilitated or accelerated by the presence of high cortisol concentrations in the heart. This thesis is supported by the considerably higher relative heart weights in the cortisol groups and is in agreement with observations reported by other authors.Dedicated to Professor Dr. W. Doerr on the occasion of his 65th birthdayThe results have been partially reported in 1977 (cf. G. Mall and H. Reinhard, Verh. Dtsch. Ges. Path. 61, 445)This investigation was supported by the Sonderforschungsbereich 90 of the Deutsche Forschungsgemeinschaft. 相似文献
35.
36.
Christian Stock Birgit Gassner Christof R. Hauck Hannelore Arnold Sabine Mally Johannes A. Eble Peter Dieterich Albrecht Schwab 《The Journal of physiology》2005,567(1):225-238
Their glycolytic metabolism imposes an increased acid load upon tumour cells. The surplus protons are extruded by the Na+ /H+ exchanger (NHE) which causes an extracellular acidification. It is not yet known by what mechanism extracellular pH (pHe ) and NHE activity affect tumour cell migration and thus metastasis. We studied the impact of pHe and NHE activity on the motility of human melanoma (MV3) cells. Cells were seeded on/in collagen I matrices. Migration was monitored employing time lapse video microscopy and then quantified as the movement of the cell centre. Intracellular pH (pHi ) was measured fluorometrically. Cell–matrix interactions were tested in cell adhesion assays and by the displacement of microbeads inside a collagen matrix. Migration depended on the integrin α2β1. Cells reached their maximum motility at pHe ∼7.0. They hardly migrated at pHe 6.6 or 7.5, when NHE was inhibited, or when NHE activity was stimulated by loading cells with propionic acid. These procedures also caused characteristic changes in cell morphology and pHi . The changes in pHi , however, did not account for the changes in morphology and migratory behaviour. Migration and morphology more likely correlate with the strength of cell–matrix interactions. Adhesion was the strongest at pHe 6.6. It weakened at basic pHe , upon NHE inhibition, or upon blockage of the integrin α2β1. We propose that pHe and NHE activity affect migration of human melanoma cells by modulating cell–matrix interactions. Migration is hindered when the interaction is too strong (acidic pHe ) or too weak (alkaline pHe or NHE inhibition). 相似文献
37.
Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis 总被引:13,自引:0,他引:13
Döhner H Stilgenbauer S Döhner K Bentz M Lichter P 《Journal of molecular medicine (Berlin, Germany)》1999,77(2):266-281
In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40–50% of tumors
when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration,
followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the ”14q+” marker are associated
with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal
karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations
in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells
but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most
frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1,
trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more
accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q
deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether
trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic
techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome
aberrations in B-CLL.
Received: 2 February 1998 / Accepted: 31 March 1998 相似文献
38.
Leen Van Langendonck Albrecht L. Claessens Johan Lefevre Martine Thomis Renaat Philippaerts Katrien Delvaux Roeland Lysens Bavo Vanden Eynde Gaston Beunen 《American journal of human biology》2002,14(6):735-742
The association between bone mass, body structure, and body composition was explored in 156 men, 40 years of AGE . Bone mineral density (total body, lumbar spine, left arm, and left leg) was obtained by dual‐energy X‐ray absorptiometry (DXA; Hologic QDR 4500A). Body structure was determined from a battery of anthropometric dimensions with a principal components analysis. Body composition was estimated with DXA. From the 24 anthropometric dimensions, three components were extracted and identified as muscle, fat, and skeletal length. Significant correlations between the muscle component and all BMD measurements (r = 0.28–0.44) were obtained. Except for BMD of the left arm, which correlated significantly, but negatively, with the fat component (r = ?0.16), no significant relations were found between the fat component and BMD. There were significant correlations between lean mass, fat mass, and BMD measurements. The correlations were higher between lean mass and BMD (r = 0.22–0.44) than between fat mass and BMD (r = 0.08–0.24). The multiple regression analysis revealed that except for BMD of the left arm only lean mass or the muscle component, and not fat mass or the fat component, were independent predictors of BMD. It is concluded that the principal anthropometric determinant of BMD in middle‐aged men is lean mass or muscle. Am. J. Hum. Biol. 14:735–742, 2002. © 2002 Wiley‐Liss, Inc. 相似文献
39.
T. Danker Birgit Gaßner Hans Oberleithner Albrecht Schwab 《Pflügers Archiv : European journal of physiology》1996,433(1-2):71-76
Madin Darby canine kidney cells transformed by alkaline stress (MDCK-F cells) constitutively migrate at a rate of about 1
μm·min–1. Migration depends on the intermittent activity of a Ca2+-stimulated, 53-pS K+ channel (KCa channel) that is inhibitable by charybdotoxin. In the present study we examined whether this intermittent KCa channel activity results in a significant K+ loss across the plasma membrane. K+ efflux from MDCK-F cells should result in a transient increase of extracellular K+ ([K+]e) in the close vicinity of a migrating cell. However, due to the rapid diffusion of K+ ions into the virtually infinite extracellular space, such a transient increase in [K+]e was too small to be detected by conventional K+-selective electrodes. Therefore, we developed a ”shielded ion-sensitive microelectrode” (SIM) that limited diffusion to a
small compartment, formed by a shielding pipette which surrounded the tip of the K+-sensitive microelectrode. The SIM improved the signal to noise ratio by a factor of at least three, thus transient increases
of [K+]e in the vicinity of MDCK-F cells became detectable. They occurred at a rate of 1.3 min–1. The cell releases 40 fmol K+ during each burst of intermittent KCa channel activity, which corresponds to about 15% of the total cellular K+ content. Since transmembrane K+ loss must be accompanied by anion loss and therefore leads to a decrease of cell volume, these findings support the hypothesis
that intermittent volume changes are a prerequisite for the migration of MDCK-F cells.
Received: 15 April 1996 / Received after revision: 18 June 1996 / Accepted: 23 July 1996 相似文献
40.
Hubert Sch?fer Katrin Klippert Petra Meuer Bettina Borsdorf Albrecht F Kiderlen Reinhard Burger 《Journal of interferon & cytokine research》2007,27(4):305-315
Interferon-gamma (IFN-gamma) plays a key role in the induction and maintenance of immunity against intracellular infectious agents. Compared to other species, little is known about the biology of this cytokine in the guinea pig (Cavia porcellus). We found that in contrast to humans and mice, IFN-gamma in the guinea pig did not induce the antiviral state, which in other species leads to protection of IFN-gamma -stimulated fibroblasts from the cytopathic effect (CPE) of subsequent viral infections. As an alternative strategy to detect and quantify guinea pig IFN-gamma activity in vitro, a reporter system using guinea pig fibroblasts transfected with a luciferase gene, which is regulated by an IFN-stimulated response element (ISRE), was established. With the help of the highly sensitive reporter assay system, the biologic activity of recombinant guinea pig IFN-gamma (GpIFN-gamma, from prokaryotic and eukaryotic expression systems was detected. The response to both native and recombinant GpIFN-gamma was inhibited by a rabbit antiserum directed against the recombinant cytokine expressed in Escherichia coli, demonstrating structural and functional homology of native and recombinant GpIFN-gamma. Stimulation with GpIFN-gamma, obtained from transfected cells, induced upregulation of MHC class I expression in a guinea pig fibroblast line. The restricted activity of GpIFN-gamma might have implications for this species' ability to control infections with intracellular pathogens. 相似文献