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What predicts progression and regression of urinary albumin excretion in the nondiabetic population?
Brantsma AH Atthobari J Bakker SJ de Zeeuw D de Jong PE Gansevoort RT 《Journal of the American Society of Nephrology : JASN》2007,18(2):637-645
An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals. 相似文献
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Sanders LH ter Woorst FJ van der Meer AD Giebelen DJ Weightman WM 《Heart, lung & circulation》2008,17(2):139-140
The presence of a beard or lower facial hair can pose a problem during skin preparation, cervical venous line insertion and draping of a patient for a sternotomy. We demonstrate how this can be dealt within a simple and economic fashion. 相似文献
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Marlon R. Schneider Ana A. Gratao Auke Boersma Cuong Hoang-Vu Thomas Klonisch 《Experimental and molecular pathology》2010,88(1):216-218
While the EGFR and most of its ligands are expressed in the male reproductive tract, their functions in male reproduction are poorly understood. Interestingly, male transgenic mice overexpressing EGF are sterile, and transgenic mice overexpressing TGFA, another EGFR ligand, show an enlarged coagulation gland (anterior prostate) due to severe hyperplasia with focal dysplasia. We studied the male reproductive tract of transgenic mice overexpressing betacellulin (BTC-tg) under the control of a promoter conferring widespread transgene expression. Despite strong overexpression of BTC in different parts of the male reproductive tract, the gross appearance and histology of the reproductive organs of BTC-tg males were normal and the same were true for sperm parameters and the in vitro fertilization rate. Collectively, our findings demonstrate that excess of BTC exerts no deleterious effects on the structure or function of the male reproductive tract in mice and indicates unique, non-overlapping functions of specific EGFR ligands in male reproduction. 相似文献
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Heide R Beishuizen A De Groot H Den Hollander JC Van Doormaal JJ De Monchy JG Pasmans SG Van Gysel D Oranje AP;Dutch National Mastocytosis Work Group 《Pediatric dermatology》2008,25(4):493-500
Abstract: Mastocytosis is characterized by an increased number of mast cells with an abnormal growth and accumulation in one or more organs. In most children mastocytosis is limited to the skin (cutaneous mastocytosis) and often transient as compared with that in adults in whom mastocytosis is usually progressive and systemic. Generally, we recognize three more common forms of cutaneous mastocytosis: maculopapulous mastocytosis (formerly urticaria pigmentosa), mastocytoma of skin, and diffuse cutaneous mastocytosis. Childhood mastocytosis can further be divided into cutaneous mastocytosis (nonpersisting and persisting) and systemic mastocytosis (extremely rare). An approach to management using a set protocol is described in table form. In most cases of mastocytosis, only yearly checkups are necessary and no treatment is required; preventive recommendations are warranted in those individuals with systemic disease and constitutional symptoms. Symptomatic therapy is advised in only a minority of cases. This article is meant as a guideline for physicians involved in the care of children with mastocytosis and their parents. 相似文献
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Comparison of Peptide Array Substrate Phosphorylation of c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8 下载免费PDF全文
Kaushal Parikh Sander H. Diks Jurriaan H. B. Tuynman Auke Verhaar Mark Lwenberg Daan W. Hommes Jos Joore Akhilesh Pandey Maikel P. Peppelenbosch 《PLoS Clinical Trials》2009,4(7)
Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to predict kinase substrate preferences from the primary structure, hampering the understanding of kinase function in physiology and prompting the development of technologies that allow easy assessment of kinase substrate consensus sequences. Hence, we decided to explore the usefulness of phosphorylation of peptide arrays comprising of 1176 different peptide substrates with recombinant kinases for determining kinase substrate preferences, based on the contribution of individual amino acids to total array phosphorylation. Employing this technology, we were able to determine the consensus peptide sequences for substrates of both c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8, two highly homologous kinases with distinct signalling roles in cellular physiology. The results show that although consensus sequences for these two kinases identified through our analysis share important chemical similarities, there is still some sequence specificity that could explain the different biological action of the two enzymes. Thus peptide arrays are a useful instrument for deducing substrate consensus sequences and highly homologous kinases can differ in their requirement for phosphorylation events. 相似文献
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Jantine D. Jonkman-de Vries Herre Talsma Roland E. C. Henrar Jantien J. Kettenes-van den Bosch Auke Bult Jos H. Beijnen 《Cancer chemotherapy and pharmacology》1994,34(5):416-422
The aim of this study was to design a stable parenteral dosing form of the investigational cytotoxic drug, encoded EO9. EO9 exhibits poor aqueous solubility and stability characteristics. Freeze-drying was selected as the manufacturing process. Differential scanning calorimetry studies were conducted to determine the freezedrying cycle parameters. A stable lyophilized formulation of EO9 was developed. The prototype, containing 8.0 mg EO9 and 200 mg lactose/vial, was found to be the optimal formulation in terms of solubility, length of the freezedrying cycle, stability, and dosing requirements for phase I clinical trials. Quality control of the freeze-dried formulation showed that the manufacturing process does not change the integrity of EO9. Shelf-life studies demonstrated that the formulation remains stable for at least 1 year when stored at +4°C in a dark environment. 相似文献