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91.
Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis 总被引:1,自引:0,他引:1
Kanno J Kure S Narisawa A Kamada F Takayanagi M Yamamoto K Hoshino H Goto T Takahashi T Haginoya K Tsuchiya S Baumeister FA Hasegawa Y Aoki Y Yamaguchi S Matsubara Y 《Molecular genetics and metabolism》2007,91(4):384-389
Pyridoxine dependent seizure (PDS) is a disorder of neonates or infants with autosomal recessive inheritance characterized by seizures, which responds to pharmacological dose of pyridoxine. Recently, mutations have been identified in the ALDH7A1 gene in Caucasian families with PDS. To elucidate further the genetic background of PDS, we screened for ALDH7A1 mutations in five PDS families (patients 1-5) that included four Orientals. Diagnosis as having PDS was confirmed by pyridoxine-withdrawal test. Exon sequencing analysis of patients 1-4 revealed eight ALDH7A1 mutations in compound heterozygous forms: five missense mutations, one nonsense mutation, one point mutation at the splicing donor site in intron 1, and a 1937-bp genomic deletion. The deletion included the entire exon 17, which was flanked by two Alu elements in introns 16 and 17. None of the mutations was found in 100 control chromosomes. In patient 5, no mutation was found by the exon sequencing analysis. Furthermore, expression level or nucleotide sequences of ALDH7A1 mRNA in lymphoblasts were normal. Plasma pipecolic acid concentration was not elevated in patient 5. These observations suggest that ALDH7A1 mutation is unlikely to be responsible for patient 5. Abnormal metabolism of GABA/glutamate in brain has long been suggested as the underlying pathophysiology of PDS. CSF glutamate concentration was elevated during the off-pyridoxine period in patient 3, but not in patient 2 or 5. These results suggest allelic and non-allelic heterogeneities of PDS, and that the CSF glutamate elevation does not directly correlate with the presence of ALDH7A1 mutations. 相似文献
92.
目的 探究食管支架置入术(ESP)和内镜下切开术(EIM)在难治性食管癌术后吻合口狭窄治疗中的应用效果.方法 将70例难治性食管癌术后吻合口狭窄患者按照手术方式不同分为ESP组(n=41)与EIM组(n=29).对比两组患者临床疗效、吞咽困难评分及并发症发生情况.结果 两组患者总有效率比较,差异无统计学意义(P>0.05).术前,两组患者Stooler评分比较,差异无统计学意义(P>0.05);术后1个月,两组患者Stooler评分均较术前降低(P<0.05),且EIM组患者Stooler评分明显低于ESP组(P<0.01).ESP组患者术后并发症总发生率高于EIM组(P<0.05).结论 EIM和ESP治疗难治性食管癌吻合口狭窄的临床疗效相当,EIM短期内对患者吞咽困难症状改善作用明显,且具有术后并发症少等优点. 相似文献
93.
Growth inhibition of Toxoplasma gondii and Plasmodium falciparum by nanomolar concentrations of 1-hydroxy-2-dodecyl-4(1H)quinolone, a high-affinity inhibitor of alternative (type II) NADH dehydrogenases
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Saleh A Friesen J Baumeister S Gross U Bohne W 《Antimicrobial agents and chemotherapy》2007,51(4):1217-1222
Both apicomplexan parasites Toxoplasma gondii and Plasmodium falciparum lack type I NADH dehydrogenases (complex I) but instead carry alternative (type II) NADH dehydrogenases, which are absent in mammalian cells and are thus considered promising antimicrobial drug targets. The quinolone-like compound 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ) was recently described as a high-affinity inhibitor of fungal alternative NADH dehydrogenases in enzymatic assays, probably by interfering with the ubiquinol binding site of the enzyme. We describe here that HDQ effectively inhibits the replication rates of P. falciparum and T. gondii in tissue culture. The 50% inhibitory concentration (IC50) of HDQ for T. gondii was determined to be 2.4+/-0.3 nM with a growth assay based on vacuole sizes and 3.7+/-1.4 nM with a growth assay based on beta-galactosidase activity. Quantification of the P. falciparum replication rate using a fluorometric assay revealed an IC50 of 14.0+/-1.9 nM. An important feature of the HDQ structure is the length of the alkyl side chain at position 2. Derivatives with alkyl side chains of C6, C8, C12 (HDQ), and C14 all displayed excellent anti-T. gondii activity, while a C5 derivative completely failed to inhibit parasite replication. A combined treatment of T. gondii-infected cells with HDQ and the antimalarial agent atovaquone, which blocks the ubiquinol oxidation site of cytochrome b in complex III, resulted in synergism, with a calculated fractional inhibitory concentration of 0.16 nM. Interference of the mitochondrial ubiquinone/ubiquinol cycle at two different locations thus appears to be a highly effective strategy for inhibiting parasite replication. HDQ and its derivatives, particularly in combination with atovaquone, represent promising compounds with a high potential for antimalarial and antitoxoplasmal therapy. 相似文献
94.
95.
目的总结在体外循环辅助下,经右房切口治疗合并下腔静脉血栓形成的布-加氏综合征的治疗经验。方法回顾我院自2002年9月至2010年7月共计49例在体外循环辅助下,经右心房切口治疗合并下腔静脉血栓的布加氏综合征的临床病例和随访资料。结果全组病人均成功的在体外循环辅助下完成经右房切口下腔静脉狭窄段扩张及血栓取出术。术中在手指破膜后再使用3.0×4.0cm球囊进行扩张。围手术期病人无死亡,无急性肺栓塞等严重并发症的发生。术后随访0~36个月,所有病人术后症状明显缓解,腹水及下肢水肿减轻至消失。1例病人术后1年后出现再狭窄,经股静脉行下腔静脉球囊扩张后好转。全组病人术后随访未见有血栓形成。结论在体外循环下,经右房切口对于合并下腔静脉血栓的布-加氏综合征是一种安全有效的治疗方法。 相似文献
96.
Rockel B Peters J Müller SA Seyit G Ringler P Hegerl R Glaeser RM Baumeister W 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(29):10135-10140
In eukaryotes, tripeptidyl peptidase II (TPPII) is a crucial component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. It is an amino peptidase belonging to the subtilase family removing tripeptides from the free N terminus of oligopeptides. The 150-kDa subunits of Drosophila TPPII assemble into a giant proteolytic complex of 6 MDa with a remarkable architecture consisting of two segmented and twisted strands that form a spindle-shaped structure. A refined 3D model has been obtained by cryoelectron microscopy, which reveals details of the molecular architecture and, in conjunction with biochemical data, provides insight into the assembly mechanism. The building blocks of this complex are apparently dimers, within which the 150-kDa monomers are oriented head to head. Stacking of these dimers leads to the formation of twisted single strands, two of which comprise the fully assembled spindle. This spindle also forms when TPPII is heterologously expressed in Escherichia coli, demonstrating that no scaffolding protein is required for complex formation and length determination. Reciprocal interactions of the N-terminal part of subunits from neighboring strands are probably involved in the formation of the native quaternary structure, lending the TPPII spindle a stability higher than that of single strands. 相似文献
97.
98.
Enhancement of erythrocyte superoxide dismutase activity: effects on cellular oxidant defense 总被引:3,自引:0,他引:3
To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4- dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered. 相似文献
99.
Summary
An infant with neonatal severe Citrobacter koseri (formerly Citrobacter diversus) meningoencephalitis developed necrosis with multicystic regression of both hemispheres. The ventriculitis persisted over
months in spite of antibiotic therapy. The treatment succeeded with cefotaxime in a high dose (300 mg/kg/day) without surgical
intervention. The infant had been previously treated with cefotaxime (200 mg/kg/day) over 5 weeks. High levels of CSF interleukin-6
(IL-6) permitted to attribute persisting CSF pleocytosis in spite of sterile CSF cultures to chronic infection and not to
reminiscence of brain necrosis. This report reveals two main points. On the one hand, the importance of therapy monitoring
with IL-6 in CSF for the consequent treatment of Citrobacter meningitis and on the other hand, high-dose cefotaxime (300 mg/kg/day) treatment of Citrobacter ventriculitis, which succeeded without surgical intervention.
Received: October 2, 1999 · Revision accepted: February 28, 2000 相似文献
100.
Bernd Kowall Wolfgang Rathmann Guido Giani Sabine Schipf Sebastian Baumeister Henri Wallaschofski Matthias Nauck Henry Völzke 《Primary Care Diabetes》2013,7(1):25-31
AimRandom glucose is widely used in routine clinical practice. We investigated whether this non-standardized glycemic measure is useful for individual diabetes prediction.MethodsThe Study of Health in Pomerania (SHIP), a population-based cohort study in north-east Germany, included 3107 diabetes-free persons aged 31–81 years at baseline in 1997–2001. 2475 persons participated at 5-year follow-up and gave self-reports of incident diabetes. For the total sample and for subjects aged ≥50 years, statistical properties of prediction models with and without random glucose were compared.ResultsA basic model (including age, sex, diabetes of parents, hypertension and waist circumference) and a comprehensive model (additionally including various lifestyle variables and blood parameters, but not HbA1c) performed statistically significantly better after adding random glucose (e.g., the area under the receiver-operating curve (AROC) increased from 0.824 to 0.856 after adding random glucose to the comprehensive model in the total sample). Likewise, adding random glucose to prediction models which included HbA1c led to significant improvements of predictive ability (e.g., for subjects ≥50 years, AROC increased from 0.824 to 0.849 after adding random glucose to the comprehensive model + HbA1c).ConclusionsRandom glucose is useful for individual diabetes prediction, and improves prediction models including HbA1c. 相似文献