全文获取类型
收费全文 | 438篇 |
免费 | 26篇 |
国内免费 | 44篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 50篇 |
基础医学 | 33篇 |
口腔科学 | 7篇 |
临床医学 | 70篇 |
内科学 | 76篇 |
皮肤病学 | 6篇 |
神经病学 | 46篇 |
特种医学 | 79篇 |
外科学 | 34篇 |
综合类 | 7篇 |
预防医学 | 11篇 |
眼科学 | 3篇 |
药学 | 65篇 |
肿瘤学 | 16篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 9篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 9篇 |
2013年 | 12篇 |
2012年 | 12篇 |
2011年 | 8篇 |
2010年 | 18篇 |
2009年 | 8篇 |
2008年 | 13篇 |
2007年 | 37篇 |
2006年 | 19篇 |
2005年 | 18篇 |
2004年 | 14篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 10篇 |
2000年 | 17篇 |
1999年 | 10篇 |
1998年 | 20篇 |
1997年 | 21篇 |
1996年 | 26篇 |
1995年 | 10篇 |
1994年 | 21篇 |
1993年 | 16篇 |
1992年 | 16篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 16篇 |
1988年 | 11篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 12篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 6篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有508条查询结果,搜索用时 0 毫秒
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.
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
4.
C Lefeuvre P Le Corre G Dollo F Chevanne J L Burgot R Le Verge 《Journal of pharmaceutical sciences》1999,88(10):1016-1020
The biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione (5PDTT) were investigated in rabbits, after administration as a complex with sulfobutyl-ether-7-beta-cyclodextrin (SBE7-beta-CD) by intravenous and oral routes and as a micronized powder by oral route. 5PDTT had a rapid and large red blood cell partitioning that was not dependent on drug concentration either in vitro or ex vivo. The blood clearance was very high (354 +/- 131 mL/min) suggesting extrahepatic metabolism and/or nonrenal elimination and a significant volume of distribution (67 +/- 76 L). The renal clearance was 0.17% of total clearance. 5-phenyl-1,2-dithiol-3-one (5PDTO) was identified as a metabolite in blood and urine. The bioavailability of 5PDTT following administration of 5PDTT/SBE7-beta-CD complex was estimated to 41% while it was close to zero when 5PDTT was given as a micronized powder. 相似文献
5.
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
6.
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
7.
Naeve GS Vana AM Eggold JR Verge G Ling N Foster AC 《Brain research. Molecular brain research》2000,75(2):185-197
Insulin-like growth factors (IGFs) are important trophic factors during development as well as in the adult or damaged nervous system. Their trophic actions are modulated by interactions with six distinct IGF binding proteins. The mRNA expression profiles of binding proteins 2, 4 and 5 in the normal developing and adult CNS are well characterized and are shown to have distinctive, non-overlapping distributions. The IGF binding protein-6 (BP6) is also expressed in the CNS, however, details regarding its mRNA expression distribution in the developing and adult nervous system is limited. BP6 has the unique property of preferentially binding the IGF-II ligand. Coupled with the fact that this ligand is the most abundantly expressed IGF in the adult CNS, this suggests that the IGF-II/BP6 complex has a unique role in modulating IGF-II function in the adult brain. In this report the anatomical distribution of BP6 messenger RNA in the developing and adult rat nervous system is presented. In the embryonic animal the CNS expression is tightly restricted to trigeminal ganglia and, relative to the rest of the embryo, this structure has the highest expression. The expression in the forebrain and cerebellum does not occur until after postnatal day 21 and then is primarily associated with GABAergic interneurons. The highest levels of expression in the adult animal are in the hindbrain, spinal cord, cranial ganglia, and dorsal root ganglia. These nuclei in the hindbrain and periphery that express BP6 are all associated with the coordination of sensorimotor function in the cerebellum, which indicates an important role for the BP6/IGF-II complex in the function and maintenance of these systems. 相似文献
8.
9.
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
10.
Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay 总被引:6,自引:0,他引:6
The traditional coagulant assay for plasma factor XI suffers from a relatively high coefficient of variation, the need for rare congenitally deficient plasma, and a poor correlation between precision and sensitivity. We have developed a simple functional amidolytic assay for factor XI in plasma using the chromogenic substrate PyrGlu-Pro-Arg- p-nitroanilide (S-2366). After inactivation of alpha 1-antitrypsin, CI inhibitor, and other plasma protease inhibitors with CHCI3, plasma was incubated with kaolin, in the absence of added calcium, which limited the enzymes formed to those dependent on contact activation. Soybean trypsin inhibitor was used to minimize the action of kallikrein on the substrate. Once the reaction was complete, corn trypsin inhibitor was used to inactive factor XIIa, the enzyme generated by exposure of plasma to negatively charged surfaces, which had activated the factor XI. The assay is highly specific for factor XI, since plasma totally deficient in that zymogen yielded only 1%-3% of the enzymatic activity in normal plasma under identical conditions. The requirements for complete conversion of factor XI to XIa in plasma within 60 min were, respectively, factor XII, 0.6 U/ml, and high molecular weight kininogen, 0.2 U/ml. Prekallikrein was not an absolute requirement for complete activation but did accelerate the reaction. The intraassay coefficient of variation was 3.4%, and the mean of 35 normal plasmas was 1.00 U +/- 0.24 SD. In addition, a new rapid radioimmunoassay was devised using staphylococcal protein A as the precipitating agent for a complex of factor XI antigen with monospecific rabbit antibody. The mean was 1.01 U +/- 0.30 SD. The correlation coefficients for amidolytic versus coagulant and amidolytic versus radioimmunoassay were r = 0.95 for the former and 0.96 for the latter. Thus, a simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in our laboratory. 相似文献