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排序方式: 共有326条查询结果,搜索用时 15 毫秒
81.
van Boven HH; Olds RJ; Thein SL; Reitsma PH; Lane DA; Briet E; Vandenbroucke JP; Rosendaal FR 《Blood》1994,84(12):4209-4213
We studied the molecular basis and genetic heterogeneity of hereditary antithrombin (III) deficiency in nine Dutch families. Polymerase chain reaction (PCR) amplification and direct sequencing of all antithrombin gene exons and flanking intronic regions identified mutations in eight families. Given the opportunity to correlate the molecular basis with survival, we addressed the relevance of molecular defects to mortality in inherited antithrombin deficiency. The defects included single nucleotide deletions (7671 del G, 7768-69 del G) and insertions (5501 ins A, 2463 G-->TC) that lead to frameshifts, a single base substitution [5381 C-->T (129Arg-->stop)] leading to a premature termination codon, and single base substitutions resulting in amino acid substitutions [2652 A-->C (63Tyr-->Ser), 13380 T-->C (421Ile-- >Thr), and 13407 G-->T (430Cys-->Phe)]. All affected individuals were heterozygous for the defects. Previously we found in Dutch families that antithrombin deficiency did not lead to higher mortality compared with the general population. In accordance with these findings, we observed no excess mortality in the nine families [Observed:Expected, 52:52.6; standardised mortality ratio (SMR) 1.0, 95% confidence interval (CI), 0.7-1.3]. Our findings confirmed a considerable genetic heterogeneity underlying antithrombin deficiency. We therefore concluded that the lack of excess mortality in these families is not caused by a Dutch mild defect. We suggest that the longevity is not affected by molecular defects in the antithrombin gene and hypothesize that differences in mortality or natural history between families most likely result from other (genetic) risk factors. 相似文献
82.
Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene 总被引:2,自引:0,他引:2
Wong C; Antonarakis SE; Goff SC; Orkin SH; Forget BG; Nathan DG; Giardina PJ; Kazazian HH Jr 《Blood》1989,73(4):914-918
We have identified two novel RNA-splicing mutations affecting a critical nucleotide (nt) in the acceptor consensus sequences at both the IVS-1/exon 2 and IVS-2/exon 3 junctions of the human beta-globin gene. Both mutations are single nt substitutions, T to G and C to A, at position -3 adjacent to the invariant AG dinucleotide. For the IVS- 2/exon 3 mutation abnormal splicing into the cryptic splice site at IVS- 2 nt 579 is documented. Identification of these two mutations provides further support for the importance of the location of specific nucleotides within the consensus sequences in splice site selection and RNA processing. 相似文献
83.
The regulation of human factor V by a neutrophil protease 总被引:1,自引:0,他引:1
Neutrophils activated with serum opsonized zymosan, soluble heat- aggregated IgG, and ionophore A23187 in the presence of calcium release a material capable of initially activating factor V. Subsequent inactivation of factor V was only observed with neutrophil releasate derived from IgG and ionophore. In this study we examine the nature of this neutrophil activity and investigate its role in the regulation of factor V/Va. From early in the fractionation it was apparent that the cells contained different enzymes capable of cleaving factor V. The most active of these was isolated and found to be an isomer of human neutrophil elastase. The purified protease caused a dose-dependent activation of isolated factor V to a maximum of threefold. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, single-chain factor V was cleaved to form intermediates of 100 and 91 kilodaltons (kD). Coagulant activity correlated with the formation of a 97-kD heavy and 77-kD light chain. On prolonged incubation the formed factor Va(e) was inactivated in association with proteolysis of the 97-kD band to smaller peptides and cleavage of the 77-kD light chain to a molecular weight of 75 kD, which is similar to thrombin-activated factor Va light chain. Neutrophil elastase also caused rapid inactivation of thrombin- activated factor V, factor Va(t). These observations suggest that elastase cleaves factor V at sites distinct from that by thrombin and therefore represents a novel factor V activation pattern. It is proposed that upon neutrophil activation elastase is secreted into the plasma milieu to initiate factor V activation. This serves to generate small amounts of thrombin that, in turn, by positive feedback fully activates factor V and thus amplifies the coagulation reaction. 相似文献
84.
Thrombomodulin, an endothelial anticoagulant protein, is absent from the human brain 总被引:10,自引:1,他引:10
Protein C activation by thrombin is significantly accelerated by the endothelial cell cofactor, thrombomodulin. In this study, we have developed a radioimmunoassay for thrombomodulin and have measured the cofactor content in several human tissues. The assay method detects as little as 2 ng of thrombomodulin. The highest thrombomodulin content was found in lung and placenta, but the antigen was also detected in spleen, pancreas, liver, kidney, skin, heart, and aorta. Unexpectedly, thrombomodulin was absent from brain. Extracts from cerebral cortex, cerebellum, centrum semiovale, midbrain, basal ganglia, pons, and medulla were devoid of thrombomodulin. In contrast, thrombomodulin antigen is present in extracerebral intracranial vessels, including basilar and internal carotid arteries and choroid plexus, as well as in endothelium of the pia-arachnoid. 相似文献
85.
Molecular cloning of a cDNA encoding canine factor IX 总被引:9,自引:1,他引:9
Factor IX (F.IX) is a vitamin K-dependent plasma protein, a deficiency of which results in hemophilia B. A canine model of hemophilia B exists; attempts to use this model for gene transfer experiments or characterization of the hemophilic defect require elucidation of normal canine F.IX structure. We report the isolation and characterization of the coding region for canine F.IX cDNA. Canine F.IX possesses 86% identity at the amino-acid level with human F.IX. The leader peptide, Gla domain, EGF domains, and the carboxy-terminal portion of the heavy chains show extensive sequence conservation between the canine and human. All Glu residues undergoing gamma-carboxylation in humans are conserved in canines. The complete coding sequence for canine F.IX has been determined, and the derived translation product has been analyzed. A similar approach should allow identification of the causative mutation in canine hemophilia B. Furthermore, this clone may prove a valuable resource in gene transfer experiments for this disease. 相似文献
86.
Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers 总被引:2,自引:0,他引:2
Lems WF; Van Veen GJ; Gerrits MI; Jacobs JW; Houben HH; Van Rijn HJ; Bijlsma JW 《Rheumatology (Oxford, England)》1998,37(1):27-33
The administration of moderate to high doses of corticosteroids is
associated with bone loss. This probably results from the uncoupling of
bone formation (decreased) and bone resorption (unchanged or increased). We
examined the effect of low-dose (10 mg/day) prednisone (LDP) and the
possible mitigating effects of calcium and 1.25 (OH)2 vitamin D
(calcitriol) on calcium and bone metabolism in eight healthy, young male
volunteers. The study consisted of four observation periods: in the first
period, LDP was prescribed during 1 week; in the second, third and fourth
periods, calcium (500 mg/day), calcitriol (0.5 micrograms b.i.d.) and
calcium in combination with calcitriol, respectively, were added to LDP.
Bone formation was measured by means of serum osteocalcin, carboxy-terminal
propeptide of type 1 procollagen (P1CP) and alkaline phosphatase, bone
resorption by means of urinary excretion of calcium, hydroxyproline, (free
and total) pyridinoline, (free and total) deoxypyridinoline and serum
carboxy-terminal cross- linked telopeptide of type 1 collagen (1CTP).
Dietary calcium and sodium intake were maintained at a stable level during
the entire study period. Treatment with LDP led to a decrease in
osteocalcin, P1CP and alkaline phosphatase (all P < 0.01). Urinary
excretion of pyridinolines, hydroxyproline and serum 1CTP did not increase,
but remained unchanged or slightly reduced (P < 0.05), depending on the
time of measurement and the marker of bone resorption. Parathyroid hormone
(PTH) (insignificantly) increased during LDP (+19%) and LDP plus calcium
(+14%), but decreased during supplementation with calcitriol (-16%) and
calcium/calcitriol (-44%; P < 0.01). Urinary excretion of calcium
increased during treatment with LDP and calcitriol (P < 0.05) and
calcium/calcitriol (P < 0.05). It is concluded that LDP has a negative
effect on bone metabolism, since bone formation decreased while bone
resorption remained unchanged or decreased slightly. The increase in PTH
during LDP could be prevented by calcitriol combined with calcium
supplementation.
相似文献
87.
Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation 总被引:20,自引:2,他引:20
Euler HH; Marmont AM; Bacigalupo A; Fastenrath S; Dreger P; Hoffknecht M; Zander AR; Schalke B; Hahn U; Haas R; Schmitz N 《Blood》1996,88(9):3621-3625
Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases. 相似文献
88.
Mohammad-Khani S Otremba B Klein R Capelle HH Logemann F Bange FC Schmidt RE Stoll M 《European journal of medical research》2010,15(11):504-506
Cryptococcus neoformans is the most common cause of life threatening meningoencephalitis in HIV-infected patients. Diagnosis is based on tests for cryptoccocal antigen in serum and cerebrospinal fluid, and on culture of the organism. We present a case of AIDS-related cryptococcal meningoencephalitis unresponsive to antifungal combination therapy, despite of evidence of fungal susceptibility in vitro. Significant decreases in cryptococcal antigen titers in serum and cerebrospinal fluid did not correlate with progress in disease and fatal outcome. 相似文献
89.
90.
Renée J Detollenaere Jan den Boon Jelle Stekelenburg Akeel HH Alhafidh Robert A Hakvoort Mark E Vierhout Hugo WF van Eijndhoven 《BMC women's health》2011,11(1):4