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81.
82.
Roessler E; Belloni E; Gaudenz K; Vargas F; Scherer SW; Tsui LC; Muenke M 《Human molecular genetics》1997,6(11):1847-1853
Holoprosencephaly (HPE) is the most common brain anomaly in humans,
involving abnormal formation and septation of the developing central
nervous system. Among the heterogeneous causes of HPE, mutations in the
Sonic Hedgehog (SHH) gene have been shown to result in an autosomal
dominant form of the disorder. Here we describe a total of five different
mutations in the processing domain encoded by exon 3 of SHH in familial and
sporadic HPE. This is the first instance in humans where SHH mutations in
the domain responsible for autocatalytic cleavage and cholesterol
modification of the N-terminal signaling domain of the protein have been
observed.
相似文献
83.
84.
Layman LC; Edwards JL; Osborne WE; Peak DB; Gallup DG; Tho SP; Reindollar RH; Roach DJ; McDonough PG; Lanclos KD 《Molecular human reproduction》1997,3(4):315-320
Women with recurrent abortion, primary unexplained infertility, and
gestational trophoblastic neoplasia (GTN) manifest disordered human
chorionic gonadotrophin (HCG) secretion. Mutations in the HCG
beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG
production in these disorders. The purpose of this study was to determine
whether HCG beta gene deletions occur in women with recurrent abortion or
primary unexplained infertility, and whether HCG beta gene duplications are
present in women with GTN. DNA was extracted from 10 patients with
unexplained recurrent abortion, 10 patients with unexplained primary
infertility, 12 patients with GTN, three partners of women with GTN, and 30
controls. Southern blots were constructed and hybridized with DNA probes
for HCG beta-5 and the LH beta gene. No gene deletions were identified in
patients with recurrent abortion or primary unexplained infertility.
Likewise, no gene duplications were identified in women with GTN. A
previously described Mbol restriction fragment length polymorphism (RFLP)
was identified in both patients and controls. A new Pstl RFLP was also
characterized, but was present in patients and controls.
Deletion/duplication mutations in the HCG beta/LH beta gene complex do not
appear to be common causes of aberrant HCG production in humans with these
disorders.
相似文献
85.
86.
87.
目的:研究Down’s 综合征动物模型trisomy 16 结肠神经系发育和先天性巨结肠(HD) 病变肠管蛋白基因产物9-5(protein gene product9 .5 ,PGP9-5) 的神经表达。方法:Trisomy 16 鼠培育;细胞遗传学分析;Trisomy 16 鼠结肠和HDPGP9-5 免疫组织化学。结果:(1)Trisomy 16 鼠结肠神经系发育异常,肌间神经丛发育迟缓,粘膜下神经丛缺失,结肠末端有5 mm 的无神经节区,但结肠系膜神经发育良好;(2)HD狭窄段肠管PGP9-5 阳性神经纤维大量增生,神经节细胞缺如。结论:(1)Trisomy 16 鼠具有稳定的遗传学特征,可能伴先天性巨结肠。(2) 由于HD 狭窄段肠管神经节细胞缺失,增生的PGP9-5 阳性神经纤维是肠道外源性神经的代偿,对其神经元的性质尚有待确定。(3)HD有遗传倾向 相似文献
88.
The degradation of fibrillar type II collagen is a major feature of
cartilage destruction in rheumatoid arthritis (RA). Since collagenase 3 is
produced by chondrocytes and preferentially degrades type II cartilage
collagen, it seemed likely that this enzyme would have a prominent role in
the destruction of rheumatoid joints. Using immunolocalization techniques,
we have examined and compared the production and distributions of
collagenase 1 and collagenase 3 in cells and tissues derived from
rheumatoid knee arthroplasties. Primary cultures of chondrocytes stimulated
with interleukin-1 beta showed that most of the cells produced collagenase
1, whereas only a minority (approximately 5-10%) produced collagenase 3; a
few chondrocytes demonstrated the co-ordinate production of both enzymes.
Primary cultures of rheumatoid synoviocytes produced collagenase 1, but not
collagenase 3. Both enzymes were demonstrated in the rheumatoid lesion.
Collagenase 1 was more commonly observed in both synovium and cartilage (22
of the 28 specimens), was especially prominent at cartilage erosion sites,
and most of the positive specimens demonstrated extracellular enzyme. By
contrast, collagenase 3 was observed less frequently (7/28 specimens) and
was produced by relatively few chondrocytes and synovial cells, this
usually being much less than that observed for chondrocytes of
osteoarthritic cartilage. These observations suggest different regulatory
mechanisms for the production of collagenases 1 and 3 in the rheumatoid
lesion, and demonstrate that the distribution and production of collagenase
1 are far more prevalent than those for collagenase 3.
相似文献
89.
Hereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong 总被引:2,自引:1,他引:1
Kanno H; Wei DC; Chan LC; Mizoguchi H; Ando M; Nakahata T; Narisawa K; Fujii H; Miwa S 《Blood》1994,84(10):3505-3509
We identified four distinct point mutations in homozygous pyruvate kinase (PK) variants in Japanese and Chinese patients with chronic nonspherocytic hemolytic anemia. All gene abnormalities were missense mutations that caused single amino acid substitutions. 1261A (Q421K) and 1436A (R436H), which were identified in PK Sendai and PK Shinshu, had been found in unrelated Japanese and Amish PK variants, respectively. The clinical severity and extremely low residual erythrocyte PK activity of PK Shinshu as well as of the Amish PK might be caused partly by aberrant splicing, because the 1436A mutation changes a nucleotide at the last nucleotide in the exon 10. Recently, we diagnosed a 42-year-old Japanese woman with chronic nonspherocytic hemolytic anemia as having a homozygous PK deficiency. DNA sequencing of the variant PK gene showed a homozygous missense mutation at 1403GCT- ->GTT, resulting in a single amino acid substitution from 468la-->Val. The gene mutation is likely to impair the allostericity of this enzyme, speculated from the tertiary structure. A homozygous missense mutation in PK Hong Kong, a boy of a non-Han southern Chinese minority group, was identified in exon 7 of the human L-PK gene, 941ATT-->ACT, resulting in a single amino acid substitution from 314lle-->Thr. The R- PK activity is expected to be severely affected, because the mutated amino acid residue is located between the 313 Lys and the 315 Glu, which are very important for acid-base catalysis and magnesium binding, respectively. Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme. 相似文献
90.
JI Tang TP Shakespeare JJ Lu YH Chan KM Lee LC Wong RK Mukherjee MF Back 《Journal of Medical Imaging and Radiation Oncology》2008,52(5):497-502
The palliative radiotherapeutic management of unresectable non‐small‐cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient’s choice of Fx schedule after involvement in a decision‐making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision‐making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients’ preferences. Of 92 patients enrolled, 55% chose the longer schedule. English‐speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2–7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision‐making process. The decision board was useful in aiding decision‐making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients’ preferences, there were significant alterations of preferred schedules because of RO’s own biases. 相似文献