全文获取类型
收费全文 | 3171篇 |
免费 | 110篇 |
国内免费 | 13篇 |
学科分类
医药卫生 | 3294篇 |
出版年
2023年 | 7篇 |
2022年 | 28篇 |
2021年 | 41篇 |
2020年 | 31篇 |
2019年 | 29篇 |
2018年 | 48篇 |
2017年 | 26篇 |
2016年 | 60篇 |
2015年 | 40篇 |
2014年 | 71篇 |
2013年 | 95篇 |
2012年 | 155篇 |
2011年 | 202篇 |
2010年 | 105篇 |
2009年 | 105篇 |
2008年 | 187篇 |
2007年 | 187篇 |
2006年 | 174篇 |
2005年 | 226篇 |
2004年 | 224篇 |
2003年 | 202篇 |
2002年 | 217篇 |
2001年 | 60篇 |
2000年 | 35篇 |
1999年 | 50篇 |
1998年 | 45篇 |
1997年 | 54篇 |
1996年 | 40篇 |
1995年 | 42篇 |
1994年 | 34篇 |
1993年 | 37篇 |
1992年 | 49篇 |
1991年 | 42篇 |
1990年 | 27篇 |
1989年 | 36篇 |
1988年 | 41篇 |
1987年 | 19篇 |
1986年 | 26篇 |
1985年 | 25篇 |
1984年 | 29篇 |
1983年 | 20篇 |
1982年 | 13篇 |
1981年 | 14篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 15篇 |
1974年 | 6篇 |
1972年 | 6篇 |
1968年 | 7篇 |
1966年 | 8篇 |
排序方式: 共有3294条查询结果,搜索用时 15 毫秒
51.
Shin-ya Kuno Mitsuharu Inaki Kiyoji Tanaka Yuji Itai Katsumi Asano 《European journal of applied physiology》1994,69(4):301-304
Four well-trained combination skiers were studied through pre- and post-training for the effects of short-term intermittent training during hypoxia on muscle energetics during submaximal exercise as measured by Phosphorus-31 nuclear magnetic resonance and maximal aerobic power (
O2max). The hypoxia and training in the cold was conducted in a hypobaric chamber and comprised 60-min aerobic exercise (at an intensity equivalent to the blood lactate threshold), using a cycle ergometer or a treadmill twice a day for 4, consecutive days at 5°C, in conditions equivalent to an altitude of 2000 m (593 mm Hg). No change in
O2max was observed over the training period, while in the muscle energetics during submaximal exercise, the values of phosphocreatine/(phosphocreatine + inorganic phosphate) and intracellular pH were found to be significantly increased by training during hypoxia. During recovery, the time constant of phosphocreatine was found to have been significantly reduced [pre, 27.9 (SD 6.7) s; post, 22.5 (SD 4.7) s, P < 0.01]. The observed inhibition of phosphocreatine as well as that of intracellular pH changes after training during hypoxia and quicker recovery of phosphocreatine in submaximal exercise tests, may indicate improved oxidative capacity (i.e. a high adenosine 5-triphosphate formation rate) despite the short-term hypoxia training.
Present address: Department Life Sciences, Univ. of Tokyo, Komaba 3-8-1, Meguro-ku 153, Japan 相似文献
52.
Furukawa H Doh-ura K Sasaki K Iwaki T 《Laboratory investigation; a journal of technical methods and pathology》2004,84(7):828-835
Prion protein (PrP) is known to accumulate in some non-neuronal tissues under conditions unrelated to prion diseases. The biochemical and biological nature of such accumulated PrP molecules, however, has not been fully evaluated. In this study, we established experimental myopathy in hamsters by long-term administration of chloroquine, and we examined the nature of the PrP molecules that accumulated. PrP accumulation was immunohistochemically demonstrated in autophagic vacuoles in degenerated muscle fibers, and this was accompanied by the accumulation of other molecules related to the neuropathogenesis of prion diseases such as clathrin, cathepsin B, heparan sulfate, and apolipoprotein J. Accumulated PrP molecules were partially insoluble in detergent solution and were slightly less sensitive to proteinase K digestion than normal cellular PrP. Muscle homogenates containing these PrP molecules did not cause disease in inoculated hamsters. The findings indicate that the PrP molecules that accumulated in muscle fibers have distinct biochemical and biological properties. Therefore, experimental chloroquine myopathy is a novel and useful model to investigate the mechanism of deposition of PrP in non-neuronal tissues and might provide new insights in the pathogenesis of prion diseases. 相似文献
53.
BACKGROUND: The cyclin-dependent kinases (CDKs) CDC2 and CDK2 are key regulators of the cell cycle. The expression of the CDK alone does not necessary reflect their true activities because they are highly regulated by post-translational mechanisms. Human hepatocellular carcinoma (HCC) is one of the most common cancers in the world, but the kinase activities of CDKs in HCC have not been examined. METHODS: Here we examined the protein expression and kinase activities associated with CDC2 and CDK2 in HCC and the corresponding non-tumorous liver tissues. RESULTS: CDC2 and CDK2 are activated in HCC in over 70% and 80% of the cases, respectively, but have little correlation with clinical parameters and PCNA expression. Interestingly, PCNA was readily detectable in extracts from non-tumorous liver, but more than 60% of samples contain higher concentration of PCNA in HCC than the corresponding non-tumorous tissues. CDC2 and CDK2 are generally activated in the same HCC samples, but the extent of their activation varied significantly, suggesting that the pathways leading to the activation of CDC2 and CDK2 can be regulated independently. Both positive regulators of CDK activity like cyclins and CDKs, and negative regulators of CDK activity like p21(CIP1/WAF1) and Thr14/Tyr15 phosphorylation were up-regulated in HCC. CONCLUSION: CDC2 and CDK2 are activated in HCC, and this may be due to a complex interplay between the level of the cyclin, CDK, CDK inhibitors, and inhibitory phosphorylation. 相似文献
54.
Age‐Adjusted Glycated Albumin at Diagnosis is more Correlated with the Product of Age and Plasma Glucose than Plasma Glucose Alone in Patients with Neonatal Diabetes Mellitus 下载免费PDF全文
55.
Some families affected by von Willebrand disease type 1 show high penetrance with exceptionally low von Willebrand factor (VWF) levels. Previously, a mutation associated with this dominant phenotype, Cys1149Arg, was found to decrease the secretion of coexpressed normal VWF, and the mutation was proposed to cause intracellular retention of pro-VWF heterodimers. To demonstrate heterodimer formation, a model was developed in which subunits could be distinguished immunologically and by size. Recombinant VWF lacking domain A1 (dA1), A3 (dA3), or both (dA13) was secreted efficiently as a full range of multimers. Cotransfection of Cys1149Arg and dA13 resulted in the secretion of multimeric VWF containing about 250 kd (Cys1149Arg) and about 210 kd (dA13). Cell lysates contained pro-VWF forms of Cys1149Arg and dA13. Immunoprecipitation with an antidomain A1 antibody recovered both subunits in heterodimers, and subunit ratios were consistent with random dimerization. Similar results were obtained for cotransfection of Cys1149Arg and dA1. Normal VWF has a Cys1149-Cys1169 intrachain bond. When cotransfected with normal VWF, Cys1149Arg or the double mutant Cys1149Arg+Cys1169Ser caused a similar decrease in VWF secretion, suggesting that an unpaired Cys1169 does not explain the intracellular retention of Cys1149Arg. VWF Cys1149Arg was not secreted from BHK cells but was degraded intracellularly within about 4 hours, and the proteasome inhibitor lactacystin delayed its clearance more than 16 hours. Thus, dominant von Willebrand disease type 1 may be caused by heterodimerization of mutant and normal subunits in the endoplasmic reticulum followed by proteasomal degradation in the cytoplasm. A similar dominant negative mechanism could cause quantitative deficiencies of other multisubunit proteins. 相似文献
56.
Nin F Hibino H Doi K Suzuki T Hisa Y Kurachi Y 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(5):1751-1756
An endocochlear potential (EP) of +80 mV is essential for audition. Although the regulation of K(+) concentration ([K(+)]) in various compartments of the cochlear stria vascularis seems crucial for the formation of the EP, the mechanism remains uncertain. We have used multibarreled electrodes to measure the potential, [K(+)], and input resistance in each compartment of the stria vascularis. The stria faces two fluids, perilymph and endolymph, and contains an extracelluar compartment, the intrastrial space (IS), surrounded by two epithelial layers, the marginal cell (MC) layer and that composed of intermediate and basal cells. Fluid in the IS exhibits a low [K(+)] and a positive potential, called the intrastrial potential (ISP). We found that the input resistance of the IS was high, indicating this space is electrically isolated from the neighboring extracellular fluids. This arrangement is indispensable for maintaining positive ISP. Inhibiting the K(+) transporters of the stria by anoxia, ouabain, or bumetanide caused the [K(+)] of the IS to increase and the intracellular [K(+)] of MCs to decrease, reducing both the ISP and the EP. Calculations indicate that the ISP represents the K(+) diffusion potential across the apical membranes of intermediate cells through Ba(2+)-sensitive K(+) channels. The K(+) diffusion potential across the apical membranes of MCs also contributes to the EP. Because the EP depends on two K(+) diffusion potentials and an electrical barrier in the stria vascularis, interference with any of these elements can interrupt hearing. 相似文献
57.
Origuchi T Arima K Kawashiri SY Tamai M Yamasaki S Nakamura H Tsukada T Aramaki T Furuyama M Miyashita T Kawabe Y Iwanaga N Terada K Ueki Y Fukuda T Eguchi K Kawakami A 《Modern rheumatology / the Japan Rheumatism Association》2012,22(4):584-588
Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50?years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2?years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3?ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7?ng/ml) (p?0.05). We found that high serum MMP-3 is characteristic of patients with paraneoplastic RS3PE syndrome. 相似文献
58.
59.
Saya Yamasaki Katsumi Shigemura Kayo Osawa Koichi Kitagawa Aya Ishii K. Kuntaman Toshiro Shirakawa Takayuki Miyara Masato Fujisawa 《Journal of infection and chemotherapy》2021,27(1):55-61
IntroductionExtended spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae is a serious concern for nosocomial infection and the emergence rate in Indonesia is higher than that in developed countries. The purpose of this study was to investigate the genetic characteristics of ESBL-producing K. pneumoniae isolated from UTI patients in Indonesia.Materials and methodsWe collected K. pneumoniae resistant to ceftazidime or cefotaxime isolated from UTI patients in Dr. Soetomo's Academic Hospital in Surabaya, Indonesia in 2015. Ninety-four strains were identified as ESBL-producing bacteria by confirmation tests. The isolates were investigated by antimicrobial susceptibility testing with 20 drugs and ESBL gene detection, plasmid replicon typing and virulence genes as hypermucoviscous (HMV) strains were tested by the string test.ResultsHigh rates of resistance to ciprofloxacin (86.2%), tetracycline (80.9%) and nalidixic acid (78.7%) were observed. CTX-M-15 was the most common ESBL gene (89.4%), 33 of which also carried SHV-type ESBL. IncF was the most prevalent plasmid replicon typing (47.6%). Sixteen (17.0%) strains were judged as HMV, all of which had rmpA and more than half of which had fimH, uge, and wab. IncL/M was the most common replicon plasmid in the HMV strains, and the difference in the positive rate was statistically significant (p = 0.0024).ConclusionThis study showed the high prevalence of multiple-drug resistant and predominately CTX-M-15-positive ESBL-producing K. pneumoniae in Indonesia. There was a correlation between IncL/M and the HMV phenotype in this study. As such hypervirulent strains continue to emerge, studying their dissemination with resistance determinants is an urgent priority. 相似文献
60.
Hyoe Inomata Takehiro Watanabe Yoko Iizuka Yi-Qiang Liang Tomoji Mashimo Toru Nabika Katsumi Ikeda Kazuyuki Yanai Takanari Gotoda Yukio Yamori Mitsuaki Isobe Norihiro Kato 《Hypertension research》2005,28(3):273-281
Cardiac hypertrophy and left ventricular hypertrophy are known to be substantially controlled by genetic factors. As an experimental model, we undertook genome-wide screens for cardiac mass in F2 populations bred from the stroke-prone spontaneously hypertensive rats (SHRSP) and normal spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) of a Japanese colony. Two F2 cohorts were independently produced: F2(SHRSP x WKY) (110 male and 110 female rats) and F2(SHR x WKY) (151 male rats). The ratio of heart weight to body weight (Hw/Bw) was evaluated at 12 months of age in F2(SHRSP x WKY) after salt-loading for 7 months, and at around 15 weeks of age in F2(SHR x WKY) who had been fed a normal rat chow diet. Subsequent to an initial screen with 251 markers in F2(SHRSP x WKY) male progeny, 170 and 161 markers were selected and characterized in F2(SHRSP x WKY) female progeny and F2(SHR x WKY) male progeny, respectively. Markers from four chromosomal regions showed suggestive or significant linkage to Hw/Bw. The strongest and the most consistent linkage was found in the vicinity of D3Mgh16 on rat chromosome (RNO) 3 (a maximal log of the odds score reached 4.0 to 6.6 across the F2 populations studied). In the other three regions on RNO6, RNO10 and RNO13, the degree of linkage was more prominent in either males or females. These data provide solid evidence for a "principal" RNO3 quantitative trait loci regulating Hw/Bw in SHRSP and SHR, and also suggest the possible presence of sexual dimorphism in regard to genetic susceptibility for cardiac hypertrophy. 相似文献