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51.
Brandner S Klein MA Frigg R Pekarik V Parizek P Raeber A Glatzel M Schwarz P Rülicke T Weissmann C Aguzzi A 《Experimental physiology》2000,85(6):705-712
The prion was defined by Stanley B. Prusiner as the infectious agent that causes transmissible spongiform encephalopathies. A pathological protein accumulating in the brain of scrapie-infected hamsters was isolated in 1982 and termed prion protein (PrPSc). Its cognate gene Prnp was identified more than a decade ago by Charles Weissmann, and shown to encode the host protein PrP(C). Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology, including the understanding of the molecular basis of the species barrier for prions. By disrupting the Prnp gene, it was shown that an organism that lacks PrP(C) is resistant to infection by prions. Introduction of mutant PrP genes into PrP-deficient mice was used to investigate the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Ectopic expression of PrP in PrP knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrP knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of haemato- and lymphopoietic cells. The latter studies have allowed us to clarify some of the mechanisms of prion spread and disease pathogenesis. 相似文献
52.
Circulating leucocyte subpopulations in sedentary subjects following graded maximal exercise with hypoxia 总被引:4,自引:0,他引:4
Holger Gabriel Thomas Kullmer Lothar Schwarz Axel Urhausen Benno Weiler Petra Born Wilfried Kindermann 《European journal of applied physiology》1993,67(4):348-353
Summary Ten healthy sedentary subjects [age, 27.5 (SD 3.5) years; height, 180 (SD 5) cm; mass, 69.3 (SD 6.3) kg] performed two periods of maximal incremental graded cycle ergometer exercise in a supine position. Randomly ordered and using an open spirometric system, one exercise was carried out during normoxia [maximal oxygen consumption (
O2max)=38.6 (SD 3.5) ml·min–1·kg–1; maximal blood lactate concentration, 9.86 (SD 1.85) mmol·l–1; test duration, 22.6 (SD 2.7) min], the other during hypoxia [
O2max=33.2 (SD 3.2) ml·min–1· kg–1; maximal blood lactate concentration, 10.38 (SD 2.02) mmol·l–1; test duration, 19.7 (SD 2.8) min]. At rest, immediately (0 p) and 60 min (60 p) after exercise, counts of leucocyte subpopulations (flow cytometry), cortisol and catecholamine concentrations were determined. At 0 p in contrast to normoxia, during hypoxia there was no significant increase of granulocytes. There were no significant differences between normoxia and hypoxia in the increases from rest to 0 p in counts of monocytes, total lymphocytes and lymphocyte subpopulations [clusters of differentiation (CD), CD3+, CD4+CD45RO–, CD4+CD45RO+, CD8+CD45RO–, CD8+CD45RO+, CD3+HLA-DR+, CD3–CD16/CD56+, CD3+CD16/CD56+, CD 19+] as well as adrenaline, noradrenaline and cortisol concentrations. The counts of CD3 –CD16/CD56+-and CD8 +CD45RO+-cells increased most. At 60 p, CD3–CD16/CD56+ and CD3+CD16/CD56+-cell counts were below pre-exercise levels and under hypoxia slightly but significantly lower than under normoxia. We concluded that the exercise-induced mobilization and redistribution of most leucocyte and lymphocyte subpopulations were unimpaired under acute hypoxia at sea level. Reduced increases of granulocyte counts during the study and reduced cell numbers of natural killer cells and cytotoxic, not major histocompatibility complex-restricted T-cells, only indicated marginal effects on the immune system. 相似文献
53.
B Glick W D Perkins C Rosse M R Schwarz 《International archives of allergy and applied immunology》1975,49(3):332-340
Rabbit anti-chicken gamma-globulin was labeled with 125I and then incubated with cells from the bursa, thymus, spleen, and bone marrow of 4- and 8-week old birds. The same procedure was carried out on 11-week-old agammaglobulinemic chickens. Autoradiography revealed that the majority of large, medium, and small bursal lymphocytes bind the antibodies while labeled lymphocytes of each type in the spleen and thymus never exceeded 11 or 4 percent, respectively. Labeled medium and small lymphocytes in the bone marrow increased from 4.2 and 1.7%, respectively, at 4 weeks of age, to 9.5 and 8.8%, respectively, at 8 weeks of age. Labeled lymphocytes of all sizes were completely absent in all tissues of agammaglobulinemic chicks, including the marrow. Therefore, the increase in frequency of labeled lymphocytes in the bone marrow with age may be a result of recruitment of cells from the bursa of Fabricius. The majority of lymphocytes in the bone marrow do not label. Therefore, lymphocytes from the bone marrow may be T cells, subsets of B cells, or neither T or B cells. 相似文献
54.
Reiss J Bonin M Schwegler H Sass JO Garattini E Wagner S Lee HJ Engel W Riess O Schwarz G 《Molecular genetics and metabolism》2005,85(1):12-20
Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance. 相似文献
55.
The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth 总被引:5,自引:0,他引:5
Steinborn K Maulbetsch C Priester B Trautmann S Pacher T Geiges B Küttner F Lepiniec L Stierhof YD Schwarz H Jürgens G Mayer U 《Genes & development》2002,16(8):959-971
Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase. 相似文献
56.
Masahiro Oike Gero Schwarz Jan Sehrer Matthias Jost Volker Gerke Klaus Weber Guy Droogmans Bernd Nilius 《Pflügers Archiv : European journal of physiology》1994,428(5-6):569-576
Possible interactions of cytoskeletal elements with mechanically induced membrane currents and Ca2+ signals were studied in human endothelial cells by using a combined patch-clamp and Fura II technique. For mechanical stimulation, cells were exposed to hypotonic solution (HTS). The concomitant cell swelling activates a Cl– current, releases Ca2+ from intracellular stores and activates Ca2+ influx. To interfere with the cytoskeleton, cells were loaded either with the F-actin-stabilizing agent phalloidin (10 mol/l), or the F-actin-depolymerizing substance cytochalasin B (50 mol/l). These were administered either in the bath or the pipette solutions. The tubulin structure of the endothelial cells was modulated by taxol (50 mol/l), which supports polymerization of tubulin, or by the depolymerizing agent colcemid (10 mol/l) both applied to the bath. Immunofluorescence experiments show that under the chosen experimental conditions the cytoskeletal modifiers employed disintegrate the F-actin and microtubuli cytoskeleton. Neither of these cytoskeletal modifiers influenced the HTS-induced Cl– current. Ca2+ release was not affected by cytochalasin B, taxol or colcemid, but was suppressed if the cells were loaded with phalloidin. Depletion of intracellular Ca2+ stores by thapsigargin renders the intracellular [Ca2+] sensitive to the extracellular [Ca2+], which is indicative of a Ca2+ entry pathway activated by store depletion. Neither cytochalasin B nor phalloidin affected this Ca2+ entry. We conclude that F-actin turnover or depolymerization is necessary for Ca2+ release by mechanical activation. The tubulin network is not involved. The Ca2+ release-activated Ca2+ entry is not modulated by the F-actin cytoskeleton. 相似文献
57.
Hocher B Dembowski C Slowinski T Friese ST Schwarz A Siren AL Neumayer HH Thöne-Reineke C Bauer C Nafz B Ehrenreich H 《Journal of molecular medicine (Berlin, Germany)》2001,78(11):633-641
The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity. 相似文献
58.
Properties of mouse leukemia viruses. XI. Immunoelectron microscopic studies on viral structural antigens on the cell surface. 总被引:14,自引:0,他引:14
Immunoelectron microscopic studies confirmed most of the results of the cytotoxic tests reported by Hunsmann et al. (Hunsmann, et al. (1976). Virology69, 157–168). GP71 and P12 viral structural antigens could be demonstrated on the surface of murine C-virus-producing but not on nonproducing transformed K Balb, MSV85 and HT-1 cells. GP71 serum revealed a type- and group-specific reactivity but failed to demonstrate an interspecies antigenic determinant, probably because of its relatively low corresponding titer. P12 antiserum reacted mainly type specifically. By this method, P10, P15, and P31 antigens were not detectable in significant amounts with the possible exception of P31 antigen on the highly producing FLV-Eveline cell. GP71 antigen occurred on the viral surface as well as on nonbudding areas of the cell membrane. P12 antigen was absent on virus particles but relatively abundant on nonbudding areas of the cell surface. No difference in the distribution of type- and group-specific determinants of GP71 was recognizable, and no clusters of the antigens studied were observed on the membrane under the conditions used. Based on these results it is suggested that among the virus structural antigens only GP71 and P12 antigens are integral surface constituents of the cells investigated and that none of the antigenic determinants studied represents a murine C-virus-induced tumor-specific cell surface antigen (TSSA). The relation of viral structural antigens to cell surface and soluble antigens described earlier and the significance of the results for possible preparation of vaccines are discussed. 相似文献
59.
Schwarz C Hauser P Steininger R Regele H Heinze G Mayer G Oberbauer R 《Laboratory investigation; a journal of technical methods and pathology》2002,82(7):941-948
SUMMARY: In renal transplantation, postischemic acute renal failure (ARF) develops in more than 20% of patients. We investigated whether tubular epithelial cells obtained from donor kidneys without subsequent ARF express a different pattern of survival genes, compared with cells from kidneys exhibiting ARF. Donor kidney biopsy specimens were obtained before transplantation from eight recipients of cadaveric kidneys with primary graft function (CAD-PF), eight patients with biopsy-proven ARF without rejection (CAD-ARF), and eight recipients of living donor kidneys with primary graft function (LIV). One thousand proximal tubular epithelial cells per biopsy specimen were isolated by laser capture microdissection. Quantitative analysis of apoptosis and the apoptosis regulatory genes Bcl-2, Bcl-xL, and Bax were performed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling staining and real-time PCR, respectively. Primary cultures of human proximal tubular epithelial cells served as calibrator. The number of apoptotic cells was significantly higher in CAD-ARF compared with LIV and CAD-PF (1.5 +/- 1.1% [p < 0.05] vs. 0.3 +/- 0.2% vs. 0.4 +/- 0.2%; mean +/- SD). The apoptosis inhibitors Bcl-2 and Bcl-xL were significantly up-regulated in renal tubular cells of recipients without ARF compared with CAD-ARF. The ratios of Bcl-2/GAPDH normalized to calibrator were as follows: LIV 48 +/- 30, CAD-PF 38 +/- 55, and CAD-ARF 5 +/- 7 (p < 0.05). The corresponding ratios for Bcl-xL were as follows: LIV 6 +/- 6, CAD-PF 5 +/- 3, and CAD-ARF 1 +/- 1 (p < 0.05). No difference in the expression of the proapoptotic Bax could be observed. These data suggest that failure of proximal tubular cells to respond to injury by up-regulation of survival factors from the Bcl-2 family contributes to postischemic ARF in patients after cadaveric renal transplantation. 相似文献
60.
Efficient correction for CT image artifacts caused by objects extending outside the scan field of view 总被引:3,自引:0,他引:3
The purpose of this paper is to develop a method of eliminating CT image artifacts generated by objects extending outside the scan field of view, such as obese or inadequately positioned patients. CT projection data are measured only within the scan field of view and thus are abruptly discontinuous at the projection boundaries if the scanned object extends outside the scan field of view. This data discontinuity causes an artifact that consists of a bright peripheral band that obscures objects near the boundary of the scan field of view. An adaptive mathematical extrapolation scheme with low computational expense was applied to reduce the data discontinuity prior to convolution in a filtered backprojection reconstruction. Despite extended projection length, the convolution length was not increased and thus the reconstruction time was not affected. Raw projection data from ten patients whose bodies extended beyond the scan field of view were reconstructed using a conventional method and our extended reconstruction method. Limitations of the algorithm are investigated and extensions for further improvement are discussed. The images reconstructed by conventional filtered backprojection demonstrated peripheral bright-band artifacts near the boundary of the scan field of view. Images reconstructed with our technique were free of such artifacts and clearly showed the anatomy at the periphery of the scan field of view with correct attenuation values. We conclude that bright-band artifacts generated by obese patients whose bodies extend beyond the scan field of view were eliminated with our reconstruction method, which reduces boundary data discontinuity. The algorithm can be generalized to objects with inhomogeneous peripheral density and to true "Region of Interest Reconstruction" from truncated projections. 相似文献