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61.
62.
L S Wicker R C Boltz V Matt E A Nichols L B Peterson N H Sigal 《European journal of immunology》1990,20(10):2277-2283
The effects of the immunosuppressants cyclosporin A (CsA), FK506 and rapamycin have been compared using murine B cells activated with a variety of mitogens. FK506 is a macrolide antibiotic that has been recently shown to inhibit T cell activation by a mechanism that appears similar to that of CsA. Rapamycin is a macrolide structurally related to FK506 whose mechanism of T cell suppression appears to be distinct from that of FK506 and CsA. While CsA and FK506 were found to preferentially inhibit B cell activation caused by stimuli which induce a rise in intracellular calcium, rapamycin partially inhibited activation by all stimuli tested, including those which are not associated with a calcium flux. All three compounds were found to inhibit cell cycle progression within the G1 phase; however, the rapamycin-sensitive event within G1 was completed earlier than the G1 events inhibited by CsA and FK506. In addition, inhibition of anti-IgM-activated B cells with CsA and FK506, but not with rapamycin, resulted in cell death. These data suggest that although CsA, FK506 and rapamycin are all inhibitors of B cell activation, the inhibitory activity of rapamycin can be clearly distinguished from that of CsA and FK506. Although the suppressive effects of CsA and FK506 on B cell proliferation were nearly identical in this study, their biological activities were distinguishable since FK506, but not CsA, could antagonize rapamycin-mediated suppression. 相似文献
63.
Morse MA Garst J Osada T Khan S Hobeika A Clay TM Valente N Shreeniwas R Sutton MA Delcayre A Hsu DH Le Pecq JB Lyerly HK 《Journal of translational medicine》2005,3(1):9-8
BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1-2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors. 相似文献
64.
John D Kriesel Deanna A Sutton Susan Schulman Annette W Fothergill Michael G Rinaldi 《Medical mycology》2008,46(6):607-610
We report a case of a life-threatening, recurrent, and azole-resistant pulmonary coccidioidomycosis in a patient receiving long-term fluconazole therapy for a history of coccidioidal meningitis. Since this diagnosis, the patient has received weekly amphotericin B for more than four years and remains in remission with a stable serum Coccidioides complement fixation antibody titer. 相似文献
65.
Elizabeth K. McLean A. E. M. McLean P. M. Sutton 《International journal of experimental pathology》1969,50(5):502-506
An improved method for production of cirrhosis of the liver in rats is described. Rats are given CCl4 and phenobarbitone simultaneously. The method doubles the yield of cirrhotic animals and halves the time taken for their production, in comparison with CCl4 alone.CCl4 inhalation results in fewer intercurrent deaths than oral dosing of CCl4. The cirrhosis as observed histologically is accompanied by gross nodularity of the liver, splenomegaly, portal hypertension and testicular atrophy. About 50 per cent of animals have measurable ascites. Animals killed during application of the new method show that cirrhosis develops only after 4 weeks of CCl4 dosage. 相似文献
66.
67.
Evoked Potentials in Hyperkinetic and Normal Children Under Certainty and Uncertainty: A Placebo and Methylphenidate Study 总被引:1,自引:0,他引:1
Differences between hyperkinetic children and normal children and the effects of methylphenidate on hyperkinetic children were investigated under conditions of differential attentional demands. Auditory average evoked potentials were recorded from vertex using a single/double click guessing paradigm under conditions of certainty and uncertainty. Under conditions of certainty (low attention), in which the subject was told the identity of each stimulus in advance, few significant group differences were found. Under conditions of uncertainty (high attention), in which the subject was asked to guess which stimulus would be presented, large group differences were found. In response to the second click the P200 component was found to be smaller and the N250 component was larger in hyperkinetic children than in normal children. Treatment with methylphenidate “normalized” the evoked potentials of the hyperkinetic children making them more like those of normal children. The findings are believed: 1) to reflect the deficit in attention observed behaviorally in hyperkinetic children, 2) to support a model of hypoarousal in hyperkinetic children, and 3) to reflect the behavioral “normalization” observed in hyperkinetic children treated with melhylphenidate. 相似文献
68.
Bernard R Labelle V Negre P Tardieu S Azulay JP Malzac P Mattéi JF Leguern E Philip N Lévy N 《European journal of human genetics : EJHG》2000,8(3):229-235
Charcot-Marie-Tooth disease, type 1A (CMT1A) is caused in most cases by a 1.5 Mb duplication on chromosome 17p11.2 arising after unequal crossing-over between repeated sequences called CMT1A-REPs, flanking the 1.5 Mb unit. A 3.2 kb recombination hot spot has been defined, resulting in a junction fragment between EcoRI (distal CMT1A-REP) and SacI (proximal CMT1A-REP). This was further reduced to a 1.7kb EcoRI-NsiI fragment, and recently to a 731 bp hot spot region within this fragment. We describe the CMT1A-REPs-based PCR method used to identify CMT1A duplications and report on a family case in which a 29-year-old pregnant woman requested prenatal diagnosis for two successive pregnancies because her husband was affected with CMT1A. Our method enabled us to characterise the duplication in both foetuses and demonstrate that it arose from a rare recombination event taking place outside the 1.7 kb region. Since our approach is simple and enables the entire set of duplications occurring after recombination in the enlarged 3.2kb region including the hot spot to be detected, we suggest it might be considered for use in primary screening for pre- and postnatal diagnosis of CMT1A. 相似文献
69.
J A Biegel L B Rorke R J Packer L N Sutton L Schut K Bonner B S Emanuel 《Genes, chromosomes & cancer》1989,1(2):139-147
We have prepared karyotypes from 22 primitive neuroectodermal tumors (PNETs) from pediatric patients ranging in age from 10 months to 16 years. Twenty-one cases were newly diagnosed, primary, posterior fossa tumors. One case was a recurrent tumor in a patient previously treated with radiation. Cytogenetic results were obtained from direct preparations and/or short-term (1-10 day) culture. Three tumors had apparently normal karyotypes. Nineteen tumors demonstrated numerical and/or structural abnormalities. The most frequent structural chromosomal changes were deletions and nonreciprocal translocations. Four tumors contained double minutes. Several chromosomes appear to be nonrandomly involved in PNETs. These include chromosomes 5, 6, 11, 16, 17, and a sex chromosome. The most consistent change, however, was an i(17q), present in one-third (8/22) of the cases. Strikingly, in three of these eight tumors, the i(17q) was the only structural abnormality observed. An i(17q) is not specific for pediatric PNETs, as it is also seen in leukemias and other solid tumors. However, in PNETs it may be a primary change related to tumor development and/or progression. Clinically, there was no correlation of the cytogenetic findings with histologic features of the tumors, size of the tumor, extent of metastasis, or surgical resection. 相似文献
70.
Sarah L. Rowland-Jones Stephen H. Powis Julian Sutton Ian Mockridge Frances M. Gotch Nick Murray Ann B. Hill William M. Rosenberg John Trowsdale Andrew J. McMichael 《European journal of immunology》1993,23(8):1999-2004
In previous studies of antigen presentation through HLA-B27, we identified a healthy person whose lymphoblastoid cells do not present three B27-restricted viral epitopes to specific cytotoxic T lymphocytes (CTL), despite adequate cell surface expression of HLA-B2702 of normal sequence. Similar findings were observed in all members of his family sharing the HLA-A3-B2702 haplotype. The original donor, NW, carries HLA-B8 on his other class I haplotype, which his daughter, HW, has inherited. We now report a failure to present an HLA-B8-restricted epitope from influenza nucleoprotein following viral infection of NW cells, although exogenous added peptide is still presented normally. However, cells from HW, which do not carry the A3-B2702 haplotype, present the expected epitope after viral infection. Another B8-restricted epitope, from human immunodeficiency virus-gag, is presented equally well by both cell lines when infected with gag-vaccinia. This antigen processing phenotype does not correlate with any of the known human TAP-1 and TAP-2 polymorphisms. 相似文献