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排序方式: 共有270条查询结果,搜索用时 15 毫秒
101.
Further studies on the interaction between human platelet membrane glycoproteins IIb and IIIa in triton X-100 总被引:3,自引:0,他引:3
Analysis of human platelet membrane proteins by crossed immunoelectrophoresis (CIE) in the presence of Triton X-100 (TX-100) has previously shown that glycoproteins (GP) IIb and IIIa are located in a single immunoprecipitate, band 16.2 To investigate whether IIb and IIIa are associated in a complex, we have analyzed TX-100-solubilized 125I-labeled membrane proteins by density gradient ultracentrifugation using 10%-40% sucrose gradients containing the nonionic detergent. studies were performed using soluble proteins derived from membranes isolated in the presence or absence of EDTA. Analysis of gradient fractions by SDS-polyacrylamide gel electrophoresis showed that in the absence of divalent cation chelation, GP IIb and IIIa penetrated well into the gradient (fractions 15-17). Analysis of fractions 15-17 by CIE revealed the presence of band 16. In contrast, when the membrane proteins were incubated with EDTA prior to or after TX-100 solubilization, IIb and IIIa remained near the top of the gradient (fractions 8-11) and gave separate immunoprecipitates during CIE. Incubation of washed platelet lysates with leupeptin, an inhibitor of the Ca2+-dependent protease of human platelets, had no effect on the shape of the band 16 immunoprecipitate. Thus, for the first time, direct evidence has been obtained that GP IIb and IIIa may form a divalent cation-mediated complex. Calibration of the sedimentation profiles using proteins of known molecular weight suggests that the complex is of limited size. Indirect evidence suggests that the complex is a heterodimer. 相似文献
102.
Outcome of Long‐Term Bisphosphonate Therapy in McCune‐Albright Syndrome and Polyostotic Fibrous Dysplasia 下载免费PDF全文
Bas CJ Majoor Natasha M Appelman‐Dijkstra Martha Fiocco Michiel AJ van de Sande PD Sander Dijkstra Neveen AT Hamdy 《Journal of bone and mineral research》2017,32(2):264-276
McCune‐Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies, and café‐au‐lait patches. FD patients have been shown to respond favorably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long‐term. We evaluated the biochemical (bone turnover markers [BTMs]) and clinical (pain reduction) outcome of bisphosphonate therapy in 11 patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range, 2 to 25 years). Prognostic factors for treatment outcome were identified in both groups. Patients with MAS were younger at diagnosis (p = 0.001), all had precocious puberty, and four (36%) had additional growth hormone (GH) excess associated with severe craniofacial FD. Extent of skeletal disease was more severe in MAS compared to PFD. MAS patients had higher serum alkaline phosphatase (ALP) concentrations (p = 0.005), higher skeletal burden scores (p < 0.001), and more fractures (p = 0.021). MAS patients had also higher levels of FGF‐23 (p = 0.008) and higher prevalence of hypophosphatemia (p = 0.013). Twenty‐four of 30 PFD patients (80%) demonstrated a complete clinical and biochemical response within a year of starting treatment (p = 0.015), compared to only four of 11 MAS patients (36%). There were no nonresponders. In the whole group, FGF‐23, total ALP, P1NP, and CTX positively correlated with skeletal burden scores (all p ≤ 0.001), which was the only significant risk factor for an incomplete response to bisphosphonate therapy (p < 0.01). Our data suggest a beneficial and safe outcome of long‐term bisphosphonate therapy in the majority of patients with PFD, although response to therapy was limited by the higher skeletal disease burden in MAS patients. In the PFD/MAS population studied, the only identified prognostic factor that influenced the outcome of bisphosphonate therapy was a high skeletal burden score. © 2016 American Society for Bone and Mineral Research. 相似文献
103.
Impact Microindentation: Consistency of Serial Measurements and Alterations in Patients With Paget's Disease of the Tibia 下载免费PDF全文
Frank Malgo Neveen AT Hamdy Socrates E Papapoulos Natasha M Appelman‐Dijkstra 《Journal of bone and mineral research》2017,32(12):2375-2380
Impact microindentation (IMI) is a new technique for the in vivo measurement of tissue‐level properties of cortical bone in humans. To address issues related to the proper application of IMI in clinical practice and to directly examine cortical bone properties in patients with tibia pathology, we studied 11 subjects without tibia pathology and nine patients with Paget's disease of the tibia in biochemical remission after bisphosphonate treatment. Serial indentations in the tibias of both legs were performed in all subjects by a single operator until 10 adequate measurements were obtained in each tibia. In patients without Paget's disease (7 men and 4 women; mean age, 61.9 years; range, 51 to 72 years), there was no difference in mean bone material strength index (BMSi) between the dominant and nondominant leg (82.1 ± 1.3 and 81.4 ± 1.3, respectively; p = 0.606). In each individual subject studied, sequential indentations in both legs showed no trends for higher or lower values with time. The standard deviation of unnormalized bone material strength (BMSu) was also comparable between the dominant and nondominant tibia (5.3 and 4.5, respectively; p = 0.657). In patients with Paget's disease (4 men and 5 women; mean age, 69.5 years; range, 55 to 87 years), mean BMSi of the Pagetic tibia was lower, albeit nonsignificantly, than that of the contralateral nonaffected tibia (74.7 ± 1.7 and 78.7 ± 1.3, respectively; p = 0.120). In contrast to subjects without Paget's disease, the SD of adequate BMSu values was significantly larger in the Pagetic tibia compared to that of the non‐Pagetic tibia (7.6 versus 5.0, respectively, p = 0.008). These results highlight the consistency of serial IMI measurements as performed by a single operator in the presence as well as absence of tibia pathology and illustrate that the method is able to capture alterations of tissue‐level cortical bone properties in patients with Paget's disease of the tibia. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. 相似文献
104.
Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease 总被引:3,自引:2,他引:3
Bijvoet AG; van de Kamp EH; Kroos MA; Ding JH; Yang BZ; Visser P; Bakker CE; Verbeet MP; Oostra BA; Reuser AJ; van der Ploeg AT 《Human molecular genetics》1998,7(1):53-62
Glycogen storage disease type II (GSDII; Pompe disease), caused by
inherited deficiency of acid alpha-glucosidase, is a lysosomal disorder
affecting heart and skeletal muscles. A mouse model of this disease was
obtained by targeted disruption of the murine acid alpha-glucosidase gene
(Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack Gaa
mRNA and have a virtually complete acid alpha-glucosidase deficiency.
Glycogen-containing lysosomes are detected soon after birth in liver, heart
and skeletal muscle cells. By 13 weeks of age, large focal deposits of
glycogen have formed. Vacuolar spaces stain positive for acid phosphatase
as a sign of lysosomal pathology. Both male and female knockout mice are
fertile and can be intercrossed to produce progeny. The first born knockout
mice are at present 9 months old. Overt clinical symptoms are still absent,
but the heart is typically enlarged and the electrocardiogram is abnormal.
The mouse model will help greatly to understand the pathogenic mechanism of
GSDII and is a valuable instrument to explore the efficacy of different
therapeutic interventions.
相似文献
105.
Although embryo cryopreservation is routine for many mammalian species, it
is important to know how the fundamental cryobiology of these cells changes
with development. Progressive cleavage divisions result in a reduction in
the blastomere surface area available for water and cryoprotectant mass
transport. Therefore, the membrane permeability of murine oocytes, zygotes,
2-cell, 4-cell, and 8-cell embryos to water (Lp), and dimethylsulphoxide
(PDMSO), and the reflection coefficient, sigma (sigma) were determined.
Oocytes or zygotes were recovered, cumulus cells removed, then cultured
until use. Oocytes and embryos were immobilized and perfused with treatment
solutions at 24 degrees C. Osmotically induced cell volume changes over
time were videotaped followed by image analysis. The Lp values in the
presence of dimethylsulphoxide (DMSO) were 0.77, 0.81, 0.94, 0.86, and 1.10
microm/min/atm, and the PDMSO values were 1.85, 2.04, 2.41, 1.95, and
1.25x10(-3) cm/min for oocytes, zygotes, 2, 4, and 8-cell embryos
respectively. The Lp values in the presence of DMSO were significantly (P
< 0.05) higher than those in the absence of DMSO. Treating the whole
embryo as a single osmotic entity leads to significantly (P < 0.05)
elevated PDMSO estimates relative to those based upon measurements of
individual blastomeres. These data indicate that both Lp and PDMSO
estimates are lower when predicted on an individual blastomere basis. The
data also show that neither Lp nor PDMSO differ among oocytes, zygotes,
2-cell and 4-cell embryos. However, the significantly higher Lp and lower
PDMSO of the 8-cell stage support the hypothesis that fundamental
cryobiological differences may require developmental stage- specific embryo
cryopreservation protocols.
相似文献
106.
107.
Kelsell RE; Evans K; Gregory CY; Moore AT; Bird AC; Hunt DM 《Human molecular genetics》1997,6(4):597-600
We have performed genetic linkage analysis on a four generation British
family with cone-rod dystrophy. Significant linkage to the disease gene was
obtained with eight marker loci situated on chromosome 17p12-p13. A maximum
two-point lod score of 5.93 with no recombination was obtained with marker
locus D17S1844. Critical recombinants identified with flanking marker loci
placed the disease gene between D17S796/D17S938 and D17S954, an interval
estimated to be 8 cM in size. This new localisation for autosomal dominant
cone-rod dystrophy (CORD6) overlaps with regions attributed previously to
Leber's congenital amaurosis, central areolar choroidal dystrophy and
dominant cone dystrophy. Given their differences in phenotype, the most
plausible explanation would be that these different retinal disorders are
caused by mutations in different genes mapping close together within the
genome.
相似文献
108.
109.
AT Dijkstra IML Majoie JWF van Dongen H van Weelden WA van Vloten 《Journal of the European Academy of Dermatology and Venereology》2001,15(6):550-554
BACKGROUND: Most clinical studies using photodynamic therapy (PDT) with topical application of delta-aminolaevulinic acid (delta-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of delta-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. AIM: To study the efficacy of violet light in combination with topical delta-ALA PDT in the treatment of pre-malignant and malignant skin lesions. METHODS: Eight hours after 20% delta-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400-450 nm). Lesions received 10-20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. RESULTS: Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90-100% of the solitary lesions of Bowen's disease. CONCLUSIONS: delta-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin. 相似文献
110.
Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia 总被引:2,自引:1,他引:2
Pui CH; Williams DL; Raimondi SC; Rivera GK; Look AT; Dodge RK; George SL; Behm FG; Crist WM; Murphy SB 《Blood》1987,70(1):247-253
Leukemic cells from 31 (7.6%) of 409 children with newly diagnosed acute lymphoblastic leukemia (ALL) had a hypodiploid karyotype. The patients' ages ranged from 0.8 to 17 years (median, 5 years) and their initial leukocyte counts from 1.0 to 132 X 10(9)/L (median, 12.7 X 10(9)/L). Modal chromosome numbers for the leukemic stem lines were 45 in 26 cases, 28 in two cases, and 26, 36 and 43 in one case each. Seven cases had one to three additional abnormal lines due to clonal evolution. Chromosome 20 was lost most frequently (nine cases). Structural abnormalities--including chromosomal translocations (21 cases), deletions (ten cases), duplications (two cases), or inversions (one case)--were common findings; the nonrandom translocations consisted of the t(1;19)(q23;p13.3) in two pre-B cases and tdic(9;12)(p1?1;p1?2) in three cases of common ALL. When compared with hyperdiploid cases (greater than 50 chromosomes), ALL with hypodiploidy was found to have a poorer outcome and was more likely to be associated with chromosomal translocations, higher serum lactic dehydrogenase levels, and age less than 2 or greater than or equal to 10 years. Moreover, patients with hypodiploid ALL fared as poorly as those with pseudodiploid karyotypes, even though their leukocyte counts and serum lactic dehydrogenase levels were lower and they had a comparable frequency of leukemic cell translocations. Hypodiploidy is therefore an unfavorable karyotypic feature in childhood ALL. 相似文献