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81.
Liu J Zheng BS Aposhian HV Zhou YS Chen ML Zhang AH Waalkes MP. 《Journal of the peripheral nervous system : JPNS》2002,7(3):208-208
Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day. 相似文献
82.
Oscillatory motion of the normal cervical spinal cord 总被引:2,自引:0,他引:2
83.
Williamson MR; Boyd CM; McGuire EL; Angtuaco T; Westbrook KC; Lang NP; Alston J; Broadwater JR; Navab F; Bersey ML 《Radiology》1986,159(1):272-273
The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding. 相似文献
84.
V. P. Cintra C. M. Lourenço M. M. V. Rocha P. J. Tomaselli W. Marques Jr 《Acta neurologica Scandinavica》2017,136(5):541-545
Spinocerebellar ataxia type 8 (SCA8) is a progressive neurological disorder caused by the expanded repeat CTA/CTG of two overlapping genes, ATXN8OS and ATXN8, expressed bidirectionally. Normal alleles have 15‐50 repeats, and pathogenic alleles range from 71 to 1300 repeats. The disorder is relatively rare, accounting for about 2%‐5% of the autosomal dominant forms of hereditary ataxia worldwide. However, the prevalence of disease‐causing ATXN8OS/ATXN8 expansions is higher than the disease because of the reduced penetrance of the expanded allele. The aim of this study was to describe the first fully penetrant SCA8 family showing mixed Brazilian African and Amerindian origin. Eight members of this family were evaluated—the mother and seven offspring—through a complete neurological examination conducted at the Neurogenetics Clinic, HCFMRP—USP in Brazil. The number of CTA/CTG repeats was obtained after polymerase chain reaction (PCR) and fragment analysis. The haplotype analysis was conducted using a microsatellite marker, D13S1296, and four single nucleotide polymorphisms (SNPs), rs1831189, rs8002227, rs11841483, and rs72284461, all spanning a 70.1 Mb region on chromosome 13q21.3. The molecular analysis showed that the expansions ranged from 104 to 109 CTA/CTG repeats in the six affected individuals and were absent in two asymptomatic daughters (aged 53 and 40 years). Three SNPs cosegregate with the expanded alleles, confirming the connection between expansion and disease in this family. As the SCA8 diagnosis demands careful interpretation, we suggest the use of linkage analysis to observe segregation of the mutation, making more accurate its genotyping. 相似文献
85.
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87.
Objective To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle. 相似文献
88.
Nutritional assessment of pregnant adolescents: comparison of two popular classification systems 下载免费PDF全文
Janaina de Fátima Ávila Amaral Guilherme Miranda Vasconcelos Maria Regina Torloni Mauro Fisberg Isa de Pádua Cintra Sampaio Cristina Aparecida Falbo Guazzelli 《Maternal & child nutrition》2015,11(3):305-313
The objective of this study was to assess the degree of concordance between two popular classification systems [the Centers for Disease Control and Prevention (CDC)‐2000 and the Institute of Medicine (IOM)‐2009] used to categorise the nutritional status of pregnant adolescents. This cross‐sectional study involved 327 pregnant adolescents (10–19 years) booking for antenatal care at a single public maternity in São Paulo, Brazil. Participants were classified into one of four categories, by both systems according to their pre‐pregnancy body mass index and age. The CDC‐2000 system classified significantly fewer pregnant adolescents as underweight (3.7% vs. 12.5%, P < 0.0001) and significantly more adolescents as normal‐weight (86.8% vs. 75.6%, P = 0.0003) than the IOM‐2009 system. The distribution of the adolescents in the two systems differed significantly. The global rate of discordance was 13.5%. The overall concordance between the two systems was marginally good (K = 0.63), being moderate for younger (<16 years) adolescents (K = 0.52). Approximately one in every seven pregnant adolescent would be classified in a non‐corresponding category if the IOM‐2009 classification was used instead of the CDC‐2000 classification. The IOM‐2009 nutritional classification, which does not take into account age and gender, tends to overestimate the proportion of underweight adolescents, especially in the younger‐age group. The use of this classification system can lead to recommendations of higher gestational weight gain in a substantial proportion of pregnant adolescents, which could predispose to post‐partum weight retention and future obesity. 相似文献
89.
Julia ML Brotherton 《Journal of paediatrics and child health》2014,50(12):959-965
The development of efficacious prophylactic human papillomavirus vaccines provided an opportunity for the primary prevention of related infections and diseases. Certain oncogenic human papillomaviruses that preferentially infect the genital epithelium cause cervical cancer and a substantial proportion of anal, penile, vaginal, vulvar and oropharyngeal cancers. Following extensive clinical trials demonstrating their efficacy and safety, two vaccines have been in global use for over 6 years. This review summarises the accumulated evidence regarding their high level of efficacy, safety in population usage, reductions in genital warts, infections and cervical disease following their adoption, and facilitators and barriers to achieving high vaccination coverage. The review also discusses practical issues and frequently asked questions regarding duration of effect, vaccination of women treated for cervical disease and alternate vaccination schedules, as well as the need to review cervical screening strategies in the post‐ vaccination environment. 相似文献
90.
B-cell acute lymphoblastic leukemia (B-ALL), more frequently than any other B-lineage neoplasm, exhibits oligoclonal Ig heavy chain (IgH) gene rearrangement in 15% to 43% of all cases studied. To study the molecular processes that promote multiple IgH rearrangements, a comprehensive sequence analysis of a B-ALL case was performed in which seven clonal IgH gene rearrangements were identified. The genetic profiles suggested that a single leukemic progenitor clone evolved into several subclones through dual processes of variable (VH) to preexisting diversity-joining (DJH) gene segment rearrangement and VH to VH gene replacement. Predominant IgH-V usage and the uniquely rearranged clonotype-specific VHDJH region gene sequences were identified using a novel DNA-based gene amplification strategy. Polymerase chain reaction (PCR) was directed by an IgH-J generic primer and a complement of family-specific IgH-V primers that defined the major B-cell IgH-V gene usage. Clonality of rearranged VHDJH bands was substantiated by high resolution denaturant gel electrophoretic analysis. Sequence patterns of the amplified VHDJH fragments segregated into two groups defined by common DJH sequences. Partial N region homology at the VHD junction as well as shared DJH sequences firmly established VH to VHDJH gene replacement as a mechanism generating clonal evolution in one group. In the second subset, oligoclonality was propagated by independent VH gene rearrangements to a common DJH precursor. The contributions of all clonal Ig-VHDJH repertoires for each group was approximately 50% and reflected a symmetric distribution of leukemic subclones generated by either process. Thus, oligoclonal rearrangements evolved by two independent, yet seemingly contemporaneous molecular genetic mechanisms. All seven clones displayed nonfunctional Ig-VHDJH recombinations. These observations may have relevance to the recombinatorial opportunities available during normal B-cell maturation. 相似文献