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排序方式: 共有1762条查询结果,搜索用时 15 毫秒
991.
Brkanac Z Bylenok L Fernandez M Matsushita M Lipe H Wolff J Nochlin D Raskind WH Bird TD 《Archives of neurology》2002,59(8):1291-1295
BACKGROUND: The autosomal dominant spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders. Although molecular genetic studies have so far implicated 16 loci in the etiology of these diseases, approximately 30% of families with SCAs remain unlinked. OBJECTIVES: To report the location of a gene causing a "pure" autosomal dominant cerebellar ataxia in one family and to describe the clinical phenotype. PATIENTS: We have identified a 4-generation American family of English and Dutch ethnicity with a pure cerebellar ataxia displaying an autosomal dominant pattern of inheritance. The disease typically has its onset in the third and fourth decades of life, shows no evidence of anticipation, progresses slowly, and does not appear to decrease life expectancy. Clinical DNA testing excluded SCA1, 2, 3, 6, 7, and 8. METHODS: A genome-wide linkage analysis at a 10 centimorgan (cM) level was performed with samples from 26 family members (11 affected, 10 clinically unaffected at risk, and 5 spouses). RESULTS: Assuming 90% penetrance, we found suggestive evidence of linkage to chromosome 19, with a lod score of 2.49 for D19S571. More detailed mapping in this region provided a maximum 2-point lod score of 2.57 at theta = 0 for D19S254 and a maximum multipoint lod score of 4.72 at D19S926. By haplotype construction a 22-cM critical region from D19S601 to the q telomere was defined. CONCLUSIONS: We have mapped a gene for an autosomal dominant SCA to chromosome 19q13.4-qter in one family. The critical region overlaps with the locus for SCA14, a disease described in a single Japanese family and characterized by axial myoclonus. Myoclonus was not seen in the family we studied, but it remains possible that the 2 disorders are allelic variants. 相似文献
992.
Roganovic Z 《Neurosurgery》2004,55(5):1120-1129
993.
A noninvasive assessment of neurovascular coupling would be of great importance. For this reason, we simultaneously studied graded responses of visually evoked cerebral blood flow (CBF) velocity responses (VEFR) and visual-evoked potentials (VEP) to visual contrasts. The records were made from 30 healthy volunteers aged 38.0 +/- 9.6 years. The stimulus was a black-and-white checkerboard with visual contrasts (VC) of 1%, 10%, and 100%. The VEFR were measured in the posterior cerebral artery using transcranial Doppler, and the VEP were recoded from the scalp from occipital leads. To test the relationship between the VEFR and the VEP, a linear regression analysis was performed. We found that the VEFR at 100% VC were 36% higher than those at 10% VC (P < 0.01). The VEFR at 10% VC were 81% higher than those at 1% VC (P < 0.01). The VEP at 100% VC were 76% higher than those at 10% VC (P < 0.01). The VEP at 10% VC were 184% higher than those at 1% VC (P < 0.01). The linear regression showed a significant, moderate association between the VEP and the VEFR (r = 0.66, P < 0.01). The analysis of the regression slopes (b = 0.48 in older subjects vs. b = 0.58 in younger subjects) between two different age subgroups (P < 0.01) did not show any significant difference (P = 0.035). We concluded that a simultaneous recording of VEFR and VEP to graded visual contrasts could allow an assessment of neurovascular coupling. 相似文献
994.
From magic bullets to designed multiple ligands 总被引:5,自引:0,他引:5
Increasingly, it is being recognised that a balanced modulation of several targets can provide a superior therapeutic effect and side effect profile compared to the action of a selective ligand. Rational approaches in which structural features from selective ligands are combined have produced designed multiple ligands that span a wide variety of targets and target classes. A key challenge in the design of multiple ligands is attaining a balanced activity at each target of interest while simultaneously achieving a wider selectivity and a suitable pharmacokinetic profile. An analysis of literature examples reveals trends and insights that might help medicinal chemists discover the next generation of these types of compounds. 相似文献
995.
Long-term survivors in myelodysplastic syndromes 总被引:1,自引:0,他引:1
Marisavljević D Rolović Z Bosković D Colović M 《Medical oncology (Northwood, London, England)》2004,21(4):333-338
Twenty-eight of 285 patients (9.8%) with primary myelodysplastic syndrome (MDS) survived more than 5 yr (long-term survivors). There were 21 females and 7 males, median age 60 yr (range 18-84 yr). None had circulating blasts, and 14 had refractory anemia (RA), 8 RA with ringed sideroblasts (RARS) and 6 RA with excess of blasts (RAEB). Thirty-seven percent of the 27 patients who were karyotyped had an abnormal clone, but none of them had -7/7q- or complex cytogenetic abnormalities. Only one of the 13 patients tested had abnormal (i.e., "leukemic") in vitro growth of GM progenitors. During 5 yr following the diagnosis, none of the 28 patients progressed to AML. Two patients with an initial diagnosis of RA showed progression to RAEB and CMML. After 5 yr, 23 of the 28 long-term survivors had stable disease (follow-up period ranged from 64 to 216 mo). One patient progressed to AML (113 mo after diagnosis) and another to RAEBT (80 mo after diagnosis). Eight asymptomatic patients were not treated and 12 patients received only supportive therapy. Except for 6 of 8 treated patients who responded to low-dose Ara-C, danazol, androgens, or immunosuppressive treatment, prolonged survival seemed to result mainly from the natural course of the disease. Except for Valensia score (p=0.033), other scoring systems (Bournemouth, Dusseldorf, Lille, and IPSS score) proved of relatively limited value in differentiating between intermediate (2-5 yr) and long-term survivors. 相似文献
996.
Radojicic ZI Perovic SV Djordjevic ML Vukadinovic VM Djakovic N 《BJU international》2004,94(1):126-130
OBJECTIVES: To describe a technique for repairing urethral diverticula which includes neourethral reconstruction and increasing the mechanical support of the neourethra. PATIENTS AND METHODS: Between February 1995 and May 2000, 267 patients with proximal hypospadias underwent a one-stage penile skin longitudinal flap urethroplasty. The overall postoperative complication rate was 20%; a diverticulum formed in 24 patients (9%) and in all it was repaired. Diverticulectomy was carried out by de-epithelialization of excess diverticular skin, so that two subcutaneous vascularized tissue wings could be created. After re-establishing distal urethral patency and neourethral closure, the de-epithelialized diverticular wings were folded and overlapped to form a mechanical support for the neourethral ventral wall; this procedure was termed 'pseudospongioplasty'. RESULTS: There were no recurrences of diverticulum or any fistula formation. The only complication was urethral stenosis in two cases, which was successfully resolved by internal urethrotomy. CONCLUSION: Re-establishing patency and providing mechanical support are essential when repairing a urethral diverticulum. Our technique with pseudospongiosal tissue reconstruction during the repair represents a good alternative or addition to other techniques. 相似文献
997.
998.
999.
Comparison of safety and efficacy between first and second generation of angio-seal closure devices in interventional patients 总被引:2,自引:0,他引:2
Lasic Z Mehran R Dangas G Mintz G Nikolsky E Tsounias E Udani PC Adamian M Adamian J Moussa I Collins M Stone G Moses J 《The Journal of invasive cardiology》2004,16(7):356-358
Arterial closure devices are safe and effective in selected patients, with complication rates similar to or lower than manual compression. The purpose of this study was to compare the safety and efficacy of the first- and new-generation Angio-Seal devices in patients undergoing PCI. This study found that the new Angio-Seal STS Platform device can secure hemostasis after PCI in a safe and effective manner similar to the old device. The new platform is easier for the operator and for the patients. 相似文献
1000.
Synaptic basal lamina is interposed between the pre- and postsynaptic membrane of the neuromuscular junction (NMJ). This position permits deposition of basal lamina-bound NMJ components of both neuronal and muscle fibre origin. One such molecule is acetylcholinesterase (AChE). The origin of NMJ AChE has been investigated previously as the answer would elucidate the relative contributions of muscle fibers and motor neurons to NMJ formation. However, in the experimental models used in prior investigations either the neuronal or muscular components of the NMJs were removed, or the NMJs were poorly differentiated. Therefore, the question of AChE origin in the intact and functional NMJ remains open. Here, we have approached this question using an in vitro model in which motor neurons, growing from embryonic rat spinal cord explants, form well differentiated NMJs with cultured human myotubes. By immunocytochemical staining with species-specific anti-AChE antibodies, we are able to differentiate between human (muscular) and rat (neuronal) AChE at the NMJ. We observed strong signal at the NMJ after staining with human AChE antibodies, which suggests a significant muscular AChE contribution. However, a weaker, but still clearly recognizable signal is observed after staining with rat AChE antibodies, suggesting a smaller fraction of AChE was derived from motor neurons. This is the first report demonstrating that both motor neuron and myotube contribute synaptic AChE under conditions where they interact with each other in the formation of an intact and functional NMJ. 相似文献