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991.
992.
Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1 总被引:3,自引:0,他引:3
Ryan AW Thornton JM Brophy K Daly JS McLoughlin RM O'Morain C Abuzakouk M Kennedy NP Stevens FM Feighery C Kelleher D McManus R 《Tissue antigens》2005,65(2):150-155
Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population. 相似文献
993.
Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum
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Zhan B Liu S Perally S Xue J Fujiwara R Brophy P Xiao S Liu Y Feng J Williamson A Wang Y Bueno LL Mendez S Goud G Bethony JM Hawdon JM Loukas A Jones K Hotez PJ 《Infection and immunity》2005,73(10):6903-6911
We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection. 相似文献
994.
Bacillus pumilus in the induction of clindamycin-associated enterocolitis in guinea pigs. 总被引:1,自引:1,他引:1
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Antibiotic-associated enterocolitis was induced in guinea pigs by the intraperitoneal injection of clindamycin. The colonic and cecal mucosa and feces of acutely ill animals were cultured under aerobic and anaerobic conditions on 5% sheep blood agar plates and on a selective and differential medium for Clostridium difficile. All morphologically distinct colony types were isolated in pure culture and identified. A sterile cell-free filtrate of each isolate was tested for ability to induce morphological changes in cultured monolayers of mouse adrenal cells. The filtrate of a predominant isolate, Bacillus pumilus, induced an alteration of cellular morphology; the sterile filtrate of other isolates were unreactive. Toxin contained in cell-free filtrates of B. pumilus caused a syndrome identical to clindamycin-associated enterocolitis when injected intracecally into guinea pigs. The toxin had a molecular weight of 6,500 daltons as determined by molecular sieve chromatography and was inactivated with pronase, lipase, and trypsin. The minimal inhibitory concentrations of clindamycin and vancomycin for B. pumilus were 50 micrograms/ml and less than or equal to 0.4 micrograms/ml, respectively. 相似文献
995.
O'Neill BJ Brophy JM Simpson CS Sholdice MM Knutson M Ross DB Ross H Rottger J Glasgow K;Canadian Cardiovascular Society Access to Care Working Group 《The Canadian journal of cardiology》2005,21(13):1149-1155
In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for urgent cardiac catheterization and revascularization, including hospital transfer in the setting of non-ST elevation acute coronary syndromes. The literature on standards of care, wait times, wait list management and clinical trials was reviewed. A survey of all cardiac catheterization directors in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommended the following medically acceptable wait times for access to diagnostic catheterization and revascularization in patients presenting with acute coronary syndromes: for diagnostic catheterization and percutaneous coronary intervention, the target should be 24 h to 48 h for high-risk, three to five days for intermediate-risk and five to seven days for low-risk patients; for coronary artery bypass graft surgery, the target should be three to five days for high-risk, two to three weeks for intermediate-risk and six weeks for low-risk patients. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. However, some questions remain around what are the best clinical risk markers to delineate the triage categories and the utility of clinical risk scores to assist clinicians in triaging patients for invasive therapies. 相似文献
996.
997.
Coagulation factor V (FV) has been shown to be synthesized in both the liver and megakaryocytes. We now present evidence that FV can be covalently crosslinked by an enzyme originating from megakaryocytes to form polymeric multimers of factor V. The guinea pig megakaryocyte enzyme appears to be factor XIIIa since the FV-crosslinking activity (1) had an absolute requirement for Ca++, (2) was completely inhibited by iodoacetamide, 5,5'-dithiobis- (2-nitrobenzoic acid), p- chloromercuribenzene sulfonic acid, and N-ethylmaleimide, all known alkylators of the thiol group at the active site of the factor XIIIa, (3) was blocked by known pseudoamine donor substrates of factor XIIIa including dansylcadaverine and putrescine, and (4) could be directly demonstrated in the guinea pig megakaryocyte lysate by a specific activity staining procedure. No tranglutaminase was detected in guinea pig megakaryocytes in contrast to red cells and liver. A similar pattern of covalent crosslinking of human FV by purified activated human plasma factor XIII was also demonstrated. Analysis of the crosslinked products of FV formed by the guinea pig enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicates the formation of intermediate as well as higher molecular weight polymers, suggesting that the crosslinking is a stepwise polymerization process. 相似文献
998.
999.
Rackoff WR; Orazi A; Robinson CA; Cooper RJ; Alter BP; Freedman MH; Harris RE; Williams DA 《Blood》1996,88(5):1588-1593
This report examines the effect of filgrastim (granulocyte colony- stimulating factor, [G-CSF] in 12 patients with neutropenia [absolute neutrophil count [ANC] < 1,000/mm3]) caused by Fanconi anemia (FA). Two of 14 patients who were evaluated for study entry were ineligible because of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 micrograms/kg/d. All patients had an increase in their ANC at week 8 (mean increase = 15,664/mm3). The median ANC during therapy was 5,030/mm3. Eight of 10 patients who completed 40 weeks on study maintained an ANC > 1,500/mm3 on G-CSF given every-otherday. Four patients had an increase in their platelet count by week 8 without transfusion (maximum increase = 23,000 to 45,000/mm3); however, platelet counts fell toward baseline levels as the G-CSF dose was reduced. BM CFU-MK were increased at week 8 in three of four evaluable patients. Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fifth patient had a red blood cell transfusion in week 2 and then had a similar increase in hemoglobin level without subsequent transfusion. Eight of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34+ cells measured by flow cytometry. The same proportion showed increases in peripheral blood CD34+ cells. Increased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating cell nuclear antigen. Adverse experiences were mild fever (1 patient) and a new BM cytogenetic abnormality at week 40 (1 patient). This study shows that prolonged administration of G-CSF exerts a stimulatory effect on the BM of FA patients and may be used to maintain a clinically adequate ANC in these patients. G-CSF has beneficial effects on multiple hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progressive aplastic anemia. G-CSF use results in an increase in circulating CD34+ cells, a finding with important implications for future gene transfer protocols. 相似文献
1000.
Cédric BP Martin Vincent S. Martin José M. Trigo Caroline Chevarin Rafael Maldonado Latham H. Fink Kathryn A. Cunningham Michel Hamon Laurence Lanfumey Raymond Mongeau 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(3)