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41.
Rapid Report     
Coexpression of KCNQ2 and KCNQ3 channels results in a 10-fold increased current amplitude compared to that of KCNQ2 alone, suggesting the formation of heteromultimeric channels. There is no interaction of either channel with KCNQ1. We evaluated the C-terminus as a potential interaction domain by construction of chimeras with interchanged C-termini of KCNQ1, KCNQ2 and KCNQ3 and functional expression in Xenopus oocytes. The chimera of KCNQ1 with a KCNQ2 C-terminus (Q1ctQ2) showed an 8-fold increase in current amplitude, and Q1ctQ3 a 3-fold increase when coexpressed with KCNQ3 and KCNQ2, respectively, indicating that the C-terminus contains an interaction domain. To characterize this interacting region, we studied further chimeras of KCNQ1 containing different parts of the KCNQ3 C-terminus for interaction with KCNQ2. We also evaluated short sequences of the KCNQ2 C-terminus for a dominant-negative effect on Q1ctQ3. According to the results of these experiments, functional interaction of KCNQ2 and KCNQ3 requires a highly conserved region of about 80 amino acids, previously called the A-domain, plus either 40 residues downstream of the A-domain (B-domain) or the proximal C-terminus between S6 and the A-domain. Furthermore, the chimeras Q1ctQ3 and Q2ctQ3 showed > 10-fold increased current amplitudes compared to KCNQ1 or KCNQ2 alone and a strong depolarizing shift of voltage-dependent activation. The proximal part of the KCNQ3 C-terminus was necessary to produce these effects. Our results indicate that specific parts of the C-terminus enable the interaction between KCNQ2 and KCNQ3 channels and that different parts of the KCNQ3 C-terminus are important for regulating current amplitude.  相似文献   
42.
Zusammenfassung 1. Die Epithel-Bindegewebsgrenze wurde bei 36 Mammacarcinomen, einem Fibroadenom der Mamma und einer proliferierenden Mastopathie systematisch elektronenmikroskopisch untersucht.2. Während das Epithel bei Fibroadenom und Mastopathie überall durch eine geschlossene, elektronenmikroskopisch eindeutig darstellbare Basalmembran vom umgebenden Bindegewebe abgegrenzt wird, fehlt eine Basalmembran in der Regel beim Mammacarcinom.3. Die Carcinomzellen liegen dem umgebenden Bindegewebe entweder mit glatter oder unregelmäßiger Zellmembran an. Die Zerklüftung der Zelloberfläche stellt sich als submikroskopisches Äquivalent von zwei verschiedenen biologischen Vorgängen an der Tumor-Stroma-Grenze dar: 1. einer Phagocytose von Fibrin und Erythrocyten und 2. einer Antigen-Antikörperreaktion.4. Das peritumorale Bindegewebe zeigt ausnahmslos eine hochgradige Aktivitätssteigerung der Fibroblasten mit vermehrter Kollagensynthese. Außerdem treten aktivierte Muskelzellen auf. Elastische Elemente gehen zugrunde.5. Bei einem Ductuscarcinom einer 38jährigen Frau war eine peritumorale Mastocytose nachweisbar; der wachstumshemmende Effekt des Heparins wird diskutiert.6. Der (in 2 Fällen beobachtete) exzessive Lymphocytenreichtum des parablastomatösen Stromas spricht für eine lokale immunologische Tumorabwehrreaktion.7. Dem nach Entdifferenzierung der Zelle und Basalmembranverlust des Parenchyms wirksam werdenden Wachstumsdruck des Tumorgewebes mit Phagocytoseleistung als Ausdruck der Aggressivität des Malignoms begegnet das Stroma mit Stoffwechselaktivierung, Phagocytose, Faserneubildung, Antihyaluronidase-Effekt und Antikörperbildung. Die Prognose eines Tumors ist das Ergebnis komplexer, temporär differenter biologischer Faktoren.
Electron microscopic studies of the junction of tumor and connective tissue in breast carcinoma of women
Summary An electron microscopic study was made of the Tumor-connectine tissue junction of 36 breast carcinomas, of 1 fibroadenoma, and of 1 proliferating mastopathy.The basement membranes were seen in the fibroadenoma and the proliferating mastopathy but normally were lacking in the mammary gland carcinomas.The malignant epithel cells adjoined the contiguous connective tissue by either smooth or irregular cell membranes. The irregularity of the cell membranes is interpreted as the submicroscopic equivalent of two different biological processes at the junction of tumor and connective tissue: 1) the phagocytosis of fibrin and red blood cells; 2) the reaction between antigen and antibody. The connective tissue surrounding the tumor showed increased activity of fibroblasts. Collagen fibres appeard newly formed. Muscle cells with increased metabolism were found. In two cases the peritumorous tissue showed an excessive abundance of lymphocytes suggesting a local immunological reaction of the organism against neoplastic tissue.In one case mast cells were found increased in the connective tissue. A reaction of heparin against hyaluronidasis is discussed.The prognosis of a malignant tumor is the sum of many complex, temporarily different biological factors.
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43.
Heat shock protein 60 (HSP60) from Chlamydia pneumoniae was described to trigger in vitro inflammatory and cytokine responses including TNF and IL-12p40. Although it can be found in atherosclerotic plaques of patients, the stimulatory potential of chlamydial and other HSP60 in vivo is unclear. We now report that chlamydial HSP60 fails to induce TNF expression in vivo, and significant serum levels of IL-12p40 are only found upon intraperitoneal injection of high doses of HSP60 or after intravenous application. Upon purification of chlamydial HSP60 with polymyxin B-agarose columns, its ability to induce TNF secretion in vitro is much reduced. However, purified chlamydial HSP60 causes increased serum levels of the CXC chemokines KC and MIP2 in vivo, as well as a strong accumulation of polymorphonuclear neutrophils (PMN) in the peritoneal cavity upon intraperitoneal challenge. With respect to PMN accumulation, chlamydial HSP60 is more potent than endotoxin or the CpG oligonucleotide 1668. The responses observed are completely abolished in Toll-like receptor (TLR)2/4-double-deficient mice, while single-deficient mice respond almost normally. Furthermore, KC induction and PMN accumulation are largely dependent on MyD88. In conclusion, HSP60 from C. pneumoniae triggers inflammatory responses in vivo that differ from responses induced by endotoxin or CpG oligonucleotides and are dependent on TLR2 and 4.  相似文献   
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In this prospective study, the use of a culture-enhanced PCR assay for the detection of Mycoplasma pneumoniae, followed by hybridization with a specific probe (MP-HPCR) or without hybridization (MP-PCR), and the use of a nested PCR (MP-NPCR) were evaluated. Clinical samples (190 specimens) from 190 patients with respiratory complaints were incubated in culture broth overnight and then subjected to PCR. The results of the PCR were compared to those obtained by culture, the direct antigen test, and serologic testing by microparticle agglutination and by immunoblotting in unclear cases. The sensitivities were 19 CFU for MP-PCR, 1.9 CFU for MP-HPCR, and 0.019 CFU for MP-NPCR. PCR amplification of the β-globin gene was possible in 98% of cases: after dilution of the β-globin-negative samples, all samples were reactive. Correlation between negative MP-NPCR results and negative serology results was found in 89% of cases; a positive correlation was found with 10% of the patients. Samples from three immunocompromised patients were MP-NPCR positive but serologically negative. High respiratory colonization by M. pneumoniae (>105 CFU/ml) in patients with acute respiratory disease could be detected by culture, MP-PCR, and MP-NPCR. These results indicate that MP-PCR and MP-NPCR are reliable methods for the detection of M. pneumoniae in respiratory tract samples of patients with respiratory complaints.  相似文献   
48.
Localization of protein B23 in HeLa cells after treatment with actinomycin D and its analogs was studied using indirect immunofluorescence. Bright nucleolar fluorescence was observed in control HeLa cells. After treatment with actinomycin D (250 ng/ml) for 2 hr, a uniform nucleoplasmic fluorescence was observed. Similar results were obtained with the actinomycin analogs, actinomycin Z5 and actinomycin K2T. Only after a much longer incubation (24 hr) with actinomycin 4-4'-gly was nucleoplasmic fluorescence observed. Actinomycin D, actinomycin Z5, and actinomycin K2T inhibited [3H]uridine incorporation into the trichloroacetic acid insoluble fraction of HeLa cells with IC50 values of 9.5 +/- 3.2, 59.1 +/- 19.6 and 1423.3 +/- 212.2 ng/ml respectively. No inhibition of [3H]uridine incorporation was observed using actinomycin 4-4'-gly (2000 ng/ml, 2-hr incubation). The order of potency for the loss of nucleolar fluorescence and the concurrent increase in nucleoplasmic fluorescence was actinomycin D greater than actinomycin Z5 greater than actinomycin K2T greater than actinomycin 4-4'-gly, which correlated with the order of their IC50 values for inhibition of [3H]uridine incorporation. Studies of the effects of actinomycin D and its analogs on RNA synthesis and localization of protein B23 indicated that there is a direct relationship between the B23 "translocation" from nucleolus to nucleoplasm and the inhibition of RNA synthesis. At 45-55% inhibition of RNA synthesis, both nuclear and nucleolar B23 immunofluorescence were observed. At 75-85% inhibition, only a uniform nucleoplasmic fluorescence was observed.  相似文献   
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T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8+ T cell responses to systemic infection.  相似文献   
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