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91.
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
92.
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
93.
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
94.
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
95.
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
96.
Jenkins TJ Guan B Dai M Li G Lightburn TE Huang S Freeze BS Burdi DF Jacutin-Porte S Bennett R Chen W Minor C Ghosh S Blackburn C Gigstad KM Jones M Kolbeck R Yin W Smith S Cardillo D Ocain TD Harriman GC 《Journal of medicinal chemistry》2007,50(3):566-584
The design, synthesis, and structure-activity relationship development of naphthalene-derived human CCR8 antagonists is described. In vitro binding assay results of these investigations are reported, critical interactions of the antagonists with CCR8 are defined, and preliminary physicochemical and pharmacokinetic data for the naphthalene scaffold are presented. 相似文献
97.
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
Background
Pelvic organ prolapse is a common health problem, affecting up to 40% of parous women over 50 years old, with significant negative influence on quality of life. Vaginal hysterectomy is currently the leading treatment method for patients with symptomatic uterine prolapse. Several studies have shown that sacrospinous fixation in case of uterine prolapse is a safe and effective alternative to vaginal hysterectomy. However, no large randomized trials with long-term follow-up have been performed to compare efficacy and quality of life between both techniques. 相似文献98.
进展期胃癌淋巴结转移与临床病理特征的关系 总被引:3,自引:1,他引:3
目的:探讨进展期胃癌淋巴结转移与临床病理特征的关系,为临床上进行合理的淋巴结清扫提供依据。方法:对55例进展期胃癌资料进行回顾性分析,术后常规解剖原发灶及各组淋巴结,并标记和计数,分析肿瘤部位、肿瘤大小、浸润深度、分化程度及Lauren分型与淋巴结转移率的关系。结果:进展期胃癌淋巴结转移率为74.5%;U、M、L区及全胃癌淋巴结转移率为85.7%、87.5%、67.6%和83.3%,各区和全胃癌淋巴结转移率差异无统计学意义(P〉0.05);浆膜受侵的胃癌淋巴结转移率为82.5%,明显高于浆膜未受侵者(53.3%)(P〈0.05);弥漫型胃癌淋巴结转移率为83.3%,明显高于肠型(64.0%)(P〈0.05);直径〉5cm癌灶淋巴结转移率为90.0%,明显高于直径≤5cm的胃癌患者(65.7%)(P〈0.05);浸润深度、Lauren分型和肿瘤大小是影响淋巴结转移率的主要因素,其中浸润深度为独立影响因素。结论:术中淋巴结清扫范围应结合肿瘤部位、肿瘤大小、浸润深度、分化程度及Lauren分型做出判断,并考虑患者的全身情况,合理选择淋巴结清扫范围。 相似文献
99.
Synergism of atenoloi and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats 下载免费PDF全文
OBJECTIVE: This study was designed to investigate the possible synergism of atenolol and nitrendipine on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in hypertensive rats. METHOD: The dose was 20 mg/kg for atenolol, 10 mg/kg for nitrendipine and 20 + 10 mg/kg for the combination of these two drugs. In an acute study, a single dose was given via a catheter previously inserted into the stomach in spontaneously hypertensive rats (SHR). 相似文献
100.
建立测定复方红甲凝胶中乳糖酸红霉素的含量测定方法。方法:以一阶导数光谱的谷一零位值法测定乳糖酸红霉素的含量,测定波长λ谷=490±lnm。结果:回收率100.6%,RSD为3.1%,线性范围40~120μg/ml。结论:方法简便,结果准确,重现性好,适合于该制剂的含量测定。 相似文献