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1.
2.
Krushkal J; Xiong M; Ferrell R; Sing CF; Turner ST; Boerwinkle E 《Human molecular genetics》1998,7(9):1379-1383
Elevated blood pressure is an important risk factor for renal-, cerebro-
and cardiovascular diseases. We used an efficient discordant sib-pair
ascertainment scheme to investigate the impact of the distal end of the
long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing
genes for the alpha1B and beta2 adrenergic receptors and the dopamine
receptor type 1A on variation of systolic blood pressure in young
Caucasians. We measured eight highly polymorphic markers spanning this
positional candidate gene-rich region in 427 individuals from 55
three-generation pedigrees containing 69 discordant sibling pairs, and
calculated multipoint identity by descent (MIBD) probabilities. The results
of genetic linkage and association tests indicate that the region between
markers D5S2093 and D5S462 is significantly linked to one or more
polymorphic genes influencing interindividual variation in systolic blood
pressure levels. Since the alpha1B adrenergic receptor and dopamine
receptor type 1A genes are located close to these markers, these data
suggest that genetic variation in one or both of these G protein-coupled
receptors, which participate in the control of vascular tone, plays an
important role in influencing interindividual variation in systolic blood
pressure levels.
相似文献
3.
Tadokoro CE Vallochi AL Rios LS Martins GA Schlesinger D Mosca T Kuchroo VK Rizzo LV Abrahamsohn IA 《Journal of autoimmunity》2004,23(2):103-115
Trypanosoma cruzi is an intracellular parasite that induces a strong Th1-type response and immunosuppression during the acute phase of infection. To study how the infection with T. cruzi would modulate the development of an autoimmune disease, we immunized C57BL/6 mice and IL-10 or iNOS knock-out mice of the same background with the encephalitogenic MOG 35-55 peptide and infected them with T. cruzi. Our results demonstrate that infection with T. cruzi completely prevents EAE development and furthermore induces complete and lasting remission in mice that were infected with this parasite after they had developed clinical EAE. Nitric oxide and IL-10 participate in triggering the mechanisms associated with EAE suppression by the infection. Decreased lymphoproliferation and increased frequencies of Annexin-positive cells and of T cells bearing CD95, CD95L or CTLA-4 were observed in the spleen from immunized/infected mice, as well as lower IL-2 and increased TGF-beta production in comparison with only immunized mice. Our results indicate that several effector and regulatory mechanisms of the immune response that arise during the acute phase of T. cruzi infection lastingly affect the expansion and/or effector functions of encephalitogenic cells, preventing the onset or inducing complete remission of EAE. 相似文献
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5.
Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented. 相似文献
6.
Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation. 相似文献
7.
van Kranen HJ; van Iersel PW; Rijnkels JM; Beems DB; Alink GM; van Kreijl CF 《Carcinogenesis》1998,19(9):1597-1601
The variation in colorectal cancer (CRC) incidence worldwide strongly
suggests a role for dietary influences. Based on epidemiological data,
protective effects of vegetables and fruit intake on CRC are widely
claimed, while other data indicate a possible increased CRC risk from
(higher) dietary fat intake. Therefore, we have investigated single and
interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in
the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this
study, four different diets (A-D) were compared, which were either low in
fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In
addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced
by a freeze-dried VFM. The diets were balanced so that they only differed
among each other in fat/carbohydrate content and the presence of specific
plant-constituents. Because the initiation of intestinal tumors in ApcMin
mice occurs relatively early in life, exposure to the diets was started in
utero. Without the addition of VFM, mice maintained at a high-fat diet did
not develop significantly higher numbers of small or large intestinal
adenomas than mice maintained at a low-fat diet. VFM added to a low-fat
diet significantly lowered multiplicity of small intestinal polyps (from
16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male
ApcMin mice only. Strikingly, addition of VFM to female mice maintained on
a low-fat diet and to both sexes maintained on a high-fat diet
significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7
polyps/mouse). In conclusion, our results indicate that neither a lower fat
intake nor consumption of VFM included in a high-fat diet decreases the
development of polyps in mice genetically predisposed to intestinal tumor
development.
相似文献
8.
Hsuan-Chang Kuo Chien-Ning Hsu Chien-Fu Huang Mao-Hung Lo Shao-Ju Chien You-Lin Tain 《Journal of the American Society of Hypertension》2012,6(6):385-392
Arginine (ARG) metabolites are interrelated and are involved in chronic kidney disease (CKD) and cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) appears to correlate with cardiovascular outcomes. We investigated the relationship between ARG metabolites, and their combined ratios in urine, and the ABPM profiles of children and adolescents with CKD. This cross-sectional study included 45 children and adolescents (age, 5–18 years) with stage 1 to 4 CKD. Each child underwent office blood pressure (BP) measurements, 24-hour ABPM, and urinary ARG metabolite determinations. Seventy percent of children with CKD had abnormal 24-hour ABPM profiles, including nocturnal hypertension, increased BP load, and nondipping nocturnal BP. The urinary ARG-to-asymmetric dimethylarginine (ADMA) ratio was lower, and the ADMA-to-symmetric dimethylarginine (SDMA) ratio was higher in children with advanced CKD (stages 2–4) than those with stage 1 CKD. CKD patients with BP abnormalities also had reduced urinary ARG and dimethylamine (DMA) levels. The higher urinary (ADMA+SDMA)-to-ARG ratios were correlated to ABPM abnormalities, including increased systolic BP load and non-dipping nocturnal BP. ABPM abnormalities were significantly associated with a high urinary (ADMA+SDMA)-to-ARG ratio, suggesting the possible involvement of methylated ARG in the development of hypertension among children with CKD. 相似文献
9.
10.
Minasian LM; Szatrowski TP; Rosenblum M; Steffens T; Morrison ME; Chapman PB; Williams L; Nathan CF; Houghton AN 《Blood》1994,83(1):56-64
Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites. 相似文献