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1.
Molecular and genetic characterization of human cell lines resistant tol-asparaginase and albizziin 总被引:1,自引:0,他引:1
Irene L. Andrulis Rhodora Argonza A. Elizabeth L. Cairney 《Somatic Cell and Molecular Genetics》1990,16(1):59-65
Human cell lines resistant tol-asparaginase or albizziin were isolated by multistep selection of HT1080 fibrosarcoma and MIA PaCa-2 pancreatic carcinoma cells. Mutants were cross-resistant to both drugs, but more resistant to the drug used for selection. The drug-resistant cell lines expressed elevated levels of asparagine synthetase activity and protein, up to 17-fold over that of the parental cells. Enzyme overproduction was due to gene amplification in the albizziin-resistant cells, whereas increased expression without amplification was observed inl-asparaginase-resistant cells. 相似文献
2.
Andrulis IL Anton-Culver H Beck J Bove B Boyd J Buys S Godwin AK Hopper JL Li F Neuhausen SL Ozcelik H Peel D Santella RM Southey MC van Orsouw NJ Venter DJ Vijg J Whittemore AS;Cooperative Family Registry for Breast Cancer studies 《Human mutation》2002,20(1):65-73
A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP. It will continue to be important to use complementary methods for mutational analysis. 相似文献
3.
4.
Julia A Knight U Venus Onay Sean Wells Hong Li Ellen J Q Shi Irene L Andrulis Hilmi Ozcelik 《Cancer epidemiology, biomarkers & prevention》2004,13(1):146-149
There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04-2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer. 相似文献
5.
Early and late diastolic strain rate vs global longitudinal strain at rest and during dobutamine stress for the assessment of significant coronary artery stenosis in patients with a moderate and high probability of coronary artery disease
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Egle Rumbinaite M.D. Diana Zaliaduonyte‐Peksiene M.D. Ph.D. Tomas Lapinskas M.D. Ruta Zvirblyte M.D. Arnas Karuzas Ieva Jonauskiene Mindaugas Viezelis M.D. Indre Ceponiene M.D. Olivija Gustiene M.D. Ph.D. Rimvydas Slapikas M.D. Ph.D. Jolanta Justina Vaskelyte M.D. Ph.D. 《Echocardiography (Mount Kisco, N.Y.)》2016,33(10):1512-1522
6.
The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma 总被引:1,自引:0,他引:1
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Chatterjee M Rancso C Stühmer T Eckstein N Andrulis M Gerecke C Lorentz H Royer HD Bargou RC 《Blood》2008,111(7):3714-3722
Current knowledge about molecular mechanisms underlying disease progression and drug resistance in multiple myeloma (MM) is still limited. Here, we analyzed the potential pathogenetic role of the Y-box binding protein YB-1 in MM. YB-1 is a member of the cold-shock domain protein superfamily and involved in various cellular functions such as proliferation. Immunohistochemical analyses revealed that neither normal bone marrow (BM) plasma cells (PCs), premalignant PCs of patients with monoclonal gammopathy of unknown significance (MGUS), nor MM cells with a mature morphology showed expression of YB-1 in situ. In contrast, YB-1 was strongly expressed in situ in normal PC precursor blasts as well as in a MM subset and in vitro in all of the evaluated MM cell lines. The YB-1-expressing MM cells were characterized by an immature morphology and a highly proliferative phenotype as defined by Ki 67 expression. We observed that siRNA-mediated knockdown of YB-1 decreased proliferation and induced apoptosis in MM cells even in the presence of BM stromal cells. Furthermore, we found that overexpression of YB-1 mediated resistance toward doxorubicin-induced apoptosis in MM cells. Thus, YB-1 contributes to disease progression, survival, and drug resistance in MM and might therefore provide an attractive therapeutic target. 相似文献
7.
Emergency departments and crowding in United States teaching hospitals 总被引:27,自引:1,他引:27
D P Andrulis A Kellermann E A Hintz B B Hackman V B Weslowski 《Annals of emergency medicine》1991,20(9):980-986
STUDY OBJECTIVES: To assess the extent and distribution of hospital and emergency department crowding nationally. DESIGN: The research design consisted of a mailed questionnaire disseminated in the fall of 1988 to the member institutions of the National Association of Public Hospitals (NAPH) and the Council of Teaching Hospitals (COTH). TYPE OF PARTICIPANTS: Study participants included hospital administrators and ED directors from 239 of the non-Veterans Administration, general acute care, US members of COTH and NAPH. MEASUREMENTS: Key measures of hospital and ED crowding including mean ED holding times for floor and ICU beds. MAIN RESULTS: Three fourths of responding hospitals reported increases in ED visits over the preceding three years. Mean ED holding times for admitted patients were 3.5 hours (median, 2.0 hours) for a floor bed and 2.9 hours (median, 1.5 hours) for an ICU bed. Half of all hospitals noted maximum waits for floor and ICU beds of ten hours or more and seven hours or more, respectively. Measures taken by hospitals to manage crowding during August 1988 included restricting access to some types of patients (mean, 3.6 days), actively transferring patients to other hospitals (mean, 2.2 days), transfer refusal (mean, 2.8 days), and total ambulance diversion (mean, 1.6 days). CONCLUSIONS: Our study strongly suggests that ED crowding is not an isolated phenomenon; ED crowding and its attendant problems appear to affect hospitals with similar adverse effects regardless of ownership. Although our results suggest that ED crowding is concentrated in metropolitan areas and in a smaller subset of hospitals, we found instances of crowding among hospitals nationwide. 相似文献
8.
Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. 总被引:67,自引:6,他引:67
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K E Noonan C Beck T A Holzmayer J E Chin J S Wunder I L Andrulis A F Gazdar C L Willman B Griffith D D Von Hoff et al. 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(18):7160-7164
The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in vitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refractory tumors untreated with chemotherapeutic drugs. We have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clinical samples, based on the polymerase chain reaction. We have used this assay to measure MDR1 gene expression in MDR cell lines and greater than 300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expression were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of samples without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were most common among tumor types known to be relatively responsive to chemotherapy. 相似文献
9.
AbstractFor the last couple of decades, multiple emulsions were prepared either by the re-emulsification of primary emulsion or they were produced by an emulsion inversion and their technological peculiarities were widely investigated. The aim of our study was to investigate and determine the optimal technological parameters of innovative multiple emulsion, prepared directly—by addition of ethanolic rosemary extract in the presence of polymeric emulsifier—and evaluate its stability by experimental surface response design approach. The results revealed that simplified W/O/W emulsification process is stirring time and stirring speed sensitive: the change of stirring time from 5 to 15?min at 600?rpm resulted in increased viscosity (from 1705.6?±?62.2 to 3364.1?±?112.5?mPA/s) and smaller oil droplet size (from 33.09?±?1.51 to 17.81?±?0.78?μm), though the conductivity increased from 800?±?2 to 882?±?2 μS/cm (p?<?.05). The second mixing stage (1000?rpm) had a negative effect on the conductivity of W/O/W emulsion because of the inner aqueous phase encapsulation efficiency. Ethanolic rosemary extract was used as multifunctional agent: not only to form multiple emulsion but also to preserve it; microbiological assay confirmed its effectiveness. A stable W/O/W type drug delivery system was successfully created without additional technological stages, phase inversion or surfactants. 相似文献
10.
Catherine L. Forse Yildiz E. Yilmaz Dushanthi Pinnaduwage Frances P. O’Malley Anna Marie Mulligan Shelley B. Bull Irene L. Andrulis 《Breast cancer research and treatment》2013,137(3):709-719
Lymphatic invasion (LVI) is associated with disease recurrence in axillary node-negative (ANN) breast cancer. Using gene expression profiling of 105 ANN tumors, we found that podocalyxin (PODXL) was more highly expressed in tumors with LVI (LVI+) than in those without LVI (LVI?). Differences in PODXL expression were validated using real-time polymerase chain reaction as well as by immunohistochemistry in an independent set of 652 tumors on tissue microarrays. Disease-free survival (DFS) analyses were conducted for association of high PODXL protein expression with risk of distant recurrence overall and within breast cancer subtypes using both Cox and cure-rate models. High PODXL expression was associated with poor prognosis features including large tumor size, high histological grade, estrogen and progesterone receptor negativity, and with clinical alterations characteristic of the basal-like breast cancer phenotype. Surprisingly, despite having other poor prognosis characteristics, women with high PODXL expressing tumors had better long-term DFS in multivariate analysis with traditional clinicopathologic factors including LVI and HER2 status (P = 0.001). PODXL has the potential to be a useful biomarker for identifying good prognosis patients in characteristically poor prognosis breast cancer groups and may impact treatment of women with this disease. 相似文献