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排序方式: 共有406条查询结果,搜索用时 31 毫秒
1.
2.
Cytosine deaminations catalyzed by DNA cytosine
methyltransferases are unlikely to be the major cause of mutational hot spots at
sites of cytosine methylation in Escherichia coli. 总被引:5,自引:0,他引:5 下载免费PDF全文
M Wyszynski S Gabbara A S Bhagwat 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(4):1574-1578
Sites of cytosine methylation are hot spots for Cto T mutations in Escherichia coli DNA. We have developed a genetic reversionassay that allows direct selection of C to T mutations at a site of methylation.Because the mutant gene is on a plasmid, this system can be used to studymutational effects of biochemical agents in vitro as well as in vivo. Using thissystem we show that in vitro an E. coli methyltransferase can cause C to Udeaminations at a site of methylation. Reaction conditions that are known toinhibit a side reaction of the methyltransferase also suppress reversionfrequency, suggesting that this side reaction is required for deamination.Furthermore, a mutation in the enzyme that eliminates its catalytic activity butnot its ability to bind DNA eliminates the ability of the enzyme to cause C to Udeaminations. Despite this, in vivo experiments strongly suggest thatenzyme-catalyzed deaminations of cytosine do not play a major role in makingmethylation sites in E. coli hot spots for mutations. For example, althoughuracil-DNA glycosylase (Ung) suppresses the occurrence of mutations due to C toU deaminations, the frequency of C to T mutations at a methylation site remainshigh in ung+ cells. Furthermore, the reversion frequencies in ung+ and ung-cells are quite similar. 相似文献
3.
The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed. 相似文献
4.
Classical and anaplastic seminoma: difference in survival 总被引:1,自引:0,他引:1
Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma. 相似文献
5.
目的:应用酵母双杂交方法筛选BRCA2相互作用蛋白编码基因,验证其相互作用并研究其功能联系。方法:以BRCA2基因3′端片段构建酵母双杂交质粒,筛选正常人乳腺上皮细胞cDNA库,获得编码相互作用蛋白的基因,采用免疫共沉淀、哺乳细胞双杂交和荧光酶测定等方法进一步验证蛋白间相互作用和功能联系.结果:采用酵母双杂交系统筛选,获得了多个编码BRCA2相互作用蛋白的基因,其中包括已知的FHL2蛋白;免疫共沉淀和哺乳动物细胞双杂交试验显示BRCA2和FHL2在体内特异性结合,并证实FHL2在体内形成同源二聚体;转录活性分析发现BRCA2与FHL2有协同转录激活作用。结论:发现BRCA2与FHL2蛋白间相互作用和功能联系,为BRCA2功能研究提供了新的方向。 相似文献
6.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
7.
A one day old neonate with a short colon, associated exomphalos minor; bifid scrotum and ileovesical fistula is reported. 相似文献
8.
MW Lieberman R Barrios G Kala SV Kala ED Lykissa CN Ou 《Environmental health perspectives》1999,107(9):A444-A445
Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165 相似文献
9.
Upendra Kaul Ripen K Gupta Kottaram K Haridas Saligrama S Ramesh Kamal K Sethi Balbir Singh Rajiv Agarwal Ram D Yadave Tapan Ghose Rakesh R Sapra Rajiv Bajaj Madhukar Shahi Ajit Bhagwat Pramod Kumar Omen P Mathews Pratik K Soni 《Catheterization and cardiovascular interventions》2002,57(4):497-503
The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation. 相似文献
10.
Baqar Husaini Aashrai SV. Gudlavalleti Van Cain Robert Levine Majaz Moonis 《Indian Journal of Community Medicine》2015,40(4):258-263