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排序方式: 共有416条查询结果,搜索用时 15 毫秒
101.
Ackerley S James PA Kalli A French S Davies KE Talbot K 《Human molecular genetics》2006,15(2):347-354
Distal hereditary motor neuronopathies (dHMNs) are a clinically and genetically heterogeneous group of disorders in which motor neurons selectively undergo age-dependant degeneration. Mutations in the small heat-shock protein HSPB1 (HSP27) are responsible for one form of dHMN. In this study, we have analysed the effect of expressing a form of mutant HSPB1 in primary neuronal cells in culture. Mutant (P182L) but not wild-type HSPB1 led to the formation of insoluble intracellular aggregates and to the sequestration in the cytoplasm of selective cellular components, including neurofilament middle chain subunit (NF-M) and p150 dynactin. These findings suggest a possible pathogenic mechanism for HSPB1 whereby the mutation may lead to preferential motor neuron loss by disrupting selective components essential for axonal structure and transport. 相似文献
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FRANK WALTHER MD MICHAEL RADKE GABRIELE KRÜGER DIRK HOBUSCH MARLIES UHLEMANN WERNER TITTELBACH-HELMRICH HANS JOACHIM STOLPE 《Pediatrics international》1994,36(1):75-79
Therapy with benzoic acid in a case of classic neonatal non-ketotic hyperglycinaemia (NKH) was successful in stopping seizures but not in promoting mental development. Serum glycine levels were normalizable even by administering low doses of 53 mg sodium benzoate/kg body mass (BM) per day. Despite giving a higher dosage (240 mg/kg BM per day) normalization of glycine concentration in cerebrospinal fluid (CSF) was not achieved. However, seizures ceased. Restriction of protein intake (≤2 g/kg BM per day) seemed to be profitable. CSF glycine concentrations below 100 μmol/L may be sufficient to prevent seizures in older infants who have adapted to neuronal glycine exposure. No toxicity of sodium benzoate treatment was detected when administering doses of up to 470 mg/kg BM per day but side effects such as itching and hyperactivity were obvious. 相似文献
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Kalli KR Chen BK Bale LK Gernand E Overgaard MT Oxvig C Cliby WA Conover CA 《International journal of cancer. Journal international du cancer》2004,110(5):633-640
Pregnancy-Associated Plasma Protein-A (PAPP-A) proteolyses insulin-like growth factor binding protein-4 (IGFBP-4), thereby regulating local IGF availability. Reduced PAPP-A mRNA expression has been reported in ovarian cancer specimens compared to normal ovarian surface epithelial cells (OSE). To characterize PAPP-A expression and proteolytic activity in OSE, we developed a lifespan-extended human cell model using a temperature-sensitive mutant of the SV40 large T antigen (SV40LT). These OSE(tsT) cells proliferate at 34 degrees C (i.e., when SV40LT-positive), but not at 39 degrees C, a temperature at which the SV40LT is unstable (SV40LT-negative). Proteolysis of radiolabeled IGFBP-4 in conditioned media from OSE(tsT) lines was IGF-dependent and blocked by anti-PAPP-A antisera. Temperature shifts that eliminated stable SV40LT induced a 7-fold increase in PAPP-A mRNA and a 4-fold increase in protein. The converse experiment (shifting to SV40LT-positive conditions) resulted in decreased levels of PAPP-A mRNA but little change in PAPP-A protein. Nevertheless, there was a marked reduction in IGF-BP-4 proteolytic activity in medium of SV40LT-positive OSE-(tsT) cells. This decreased PAPP-A activity coincided with a nearly 20-fold increase in mRNA encoding a physiological inhibitor of PAPP-A, the precursor form of eosinophil Major Basic Protein (proMBP), and 4- to 5-fold increases in proMBP protein. Primary cultures of unmodified OSE expressed high levels of PAPP-A and undetectable proMBP, and therefore produced abundant IGFBP-4 protease activity. Short-term ovarian tumor cell cultures expressed variable levels of PAPP-A and high levels of proMBP, and consequently secreted little or no IGFBP-4 protease activity. The concurrent regulation of PAPP-A and its inhibitor, proMBP, suggests that IGFBP-4 proteolysis and local regulation of IGF availability may be altered in malignant ovarian epithelial cells. 相似文献
107.
Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy. 总被引:3,自引:0,他引:3
Lynn C Hartmann Karen H Lu Gerald P Linette William A Cliby Kimberly R Kalli David Gershenson Robert C Bast James Stec Natalia Iartchouk David I Smith Jeffrey S Ross Sebastian Hoersch Viji Shridhar James Lillie Scott H Kaufmann Edwin A Clark Andrew I Damokosh 《Clinical cancer research》2005,11(6):2149-2155
PURPOSE: Women with advanced epithelial ovarian cancer are routinely treated with platinum-paclitaxel chemotherapy following cytoreductive surgery, yet only approximately 20% achieve long-term disease-free survival. We hypothesized that differences in gene expression before treatment could distinguish patients with short versus long time to recurrence after administration of platinum-paclitaxel combination chemotherapy. EXPERIMENTAL DESIGN: To test this hypothesis, gene expression profiling of 79 primary surgically resected tumors from women with advanced-stage, high-grade epithelial ovarian cancer was done using cDNA microarrays containing 30,721 genes. Supervised learning algorithms were applied in an effort to develop a binary classifier that could discriminate women at risk for early (< or =21 months) versus late (>21 months) relapse after initial chemotherapy. RESULTS: A 14-gene predictive model was developed using a set of training samples (n = 51) and subsequently tested using an independent set of test samples (n = 28). This model correctly predicted the outcome of 24 of the 28 test samples (86% accuracy) with 95% positive predictive value for early relapse. CONCLUSIONS: Predictive markers for early recurrence can be identified for platinum-paclitaxel combination chemotherapy in primary ovarian carcinoma. The proposed 14-gene model requires further validation. 相似文献
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109.
A large number of microfilaria (MF) positive cases were reported at a Military Hospital in 1994. The epidemiological investigations included mass night blood survey, detection of sector breeding places and entomological studies. Control measures were instituted concurrently and this included treatment of positive cases, sector control measures, personal protection and health education. The mass blood survey was continued in 1995 as well to find the outcome of control measures. A total of 215 MF positive cases were detected in 1994 with MF rate of 9.63. The only MF species identified was Wuchereria bancrofti. 203% cases were in the station for less than six months. 71.3% of MF positive cases were asymptomatic. As per state health authorities, Culex quinquefasciatus was the known vector for spread of the disease in the region. However, in present study, it could not be implicated as dissection of over 200 mosquitoes of this species was negative for filarial parasite. Our study stresses the importance of close monitoring of the disease by night blood surveys and effective integrated vector control measures.KEY WORDS: Control, Epidemiology, Filariasis 相似文献
110.
Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects 总被引:1,自引:1,他引:1
Spontaneous mutation rates at the hypoxanthine-guanine phosphoribosyl
transferase (hprt) locus were measured in human cancer cell lines defective
in the mismatch repair (MMR) genes hMLH1, hPMS2, or GTBP, as well as in a
cell line carrying mutations in both hMLH1 and hPMS2. The mutation rate was
determined by quantitating mutant frequency increases within a single
culture as a function of cell division. These MMR- deficient cell lines
exhibited a 50- to 750-fold increase in mutation rate relative to a
MMR-proficient cancer cell line. From lowest to highest, the spontaneous
mutation rates relative to the MMR-gene defects studied here are as
follows: hMLH1- < GTBP- < hPMS2- < hMLH1- / hPMS2-. In addition, a
cell line in which MMR was restored by chromosome transfer exhibited a
mutation rate 12-fold below the MMR- deficient parental cell line. These
data support the notion that MMR plays an important role in controlling the
rate of spontaneous mutation and suggest that different MMR-gene defects
may vary in their ability to repair different types of DNA mismatches, thus
leading to measurable quantitative differences in spontaneous mutagenesis.
Furthermore, a difference in mutation rates was observed between a
hPMS2-defective cell line (3.1 x 10(-5) mutations/cell/generation) and two
hMLH1- defective cell lines (4.0 x 10(-6) and 7.3 x 10(-6)
mutations/cell/generation). Assuming the hPMS2- and hMLH1-gene products
only function in the proposed hMutL alpha heterodimer, then defects in
either gene should yield comparable mutation rates. These data suggest that
hPMS2 plays a critical role in MMR, while additional hMLH1 homologues or
hPMS2 alone may function to partially complement defects in hMLH1.
相似文献