全文获取类型
收费全文 | 127篇 |
免费 | 10篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 7篇 |
2012年 | 12篇 |
2011年 | 8篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 5篇 |
2007年 | 7篇 |
2006年 | 4篇 |
2004年 | 4篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1949年 | 1篇 |
1948年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有137条查询结果,搜索用时 484 毫秒
101.
102.
The purpose of this paper is to describe the background and methods of a prospective study of medical care utilization and morbidity in a fixed cohort of over 500 preschool children whose families belonged to a prepaid group practice affiliated with Yale University. Following baseline interviews with their mothers, study children were followed for 12 months between 1981 and 1982. Information concerning the subjects' contacts with the health care facility serving members of the group practice was collected from accompanying adults, attending clinicians, and medical records. Using these data, we were able to identify episodes of care, linking all clinical visits and phone calls for single occurrences of an illness or injury. The major aim of the study is to identify psychosocial determinants of pediatric utilization (for both acute and preventive care) and of childhood morbidity. The possible predictors of principal interest are factors associated with the family environment, such as social stress and strain, family structure, and different aspects of the mother's social network. The dual emphasis on both illness and behavior outcomes is based on the important interrelationship between epidemiologic and health services research, especially when examining psychosocial effects. 相似文献
103.
104.
In the recent literature, several hypotheses have been offered to explain patterns of human behavior in social environments. In particular, these patterns include ‘prosocial’ ones, such as fairness, cooperation, and collective good provision. Psychologists suggest that these prosocial behaviors are driven not by miscalculations, but by salience of social identity, in-group favoritism, emotion, or evolutionary adaptations. This paper imports psychology scholarship into an economic model and results in a sustainable solution to collective action problems without any external enforcement mechanisms. This natural mechanism of public goods provision is created, analyzed, and observed in a controlled laboratory environment using experimental techniques. 相似文献
105.
Liu T Nedrow-Byers JR Hopkins MR Berkman CE 《Bioorganic & medicinal chemistry letters》2011,21(23):7013-7016
Prostate-specific membrane antigen (PSMA), a type II transmembrane protein, has been becoming an active target for imaging and therapeutic applications for prostate cancer. Recently, the development of its various chemical inhibitor scaffolds has been explored to serve as carriers for therapeutic or diagnostic payloads targeted to PSMA-positive tumor cells. However, there have been few efforts to definitively determine the optimal length of linker between PSMA inhibitor cores and their payload molecules with regard to the affinity to PSMA and in vitro performance. In our present model study, three spacer-length varied fluorescent inhibitors (FAM-CTT-54, FAM-X-CTT-54 and FAM-PEG(8)-CTT-54) were synthesized, and further enzymatic inhibition studies displayed linker length-dependent changes in: inhibitory potency (IC(50)=0.41 nM, 0.35 nM, 1.93 nM), modes of binding (reversible, slowly reversible, irreversible), respectively. Furthermore, cell-labeling imaging revealed the spacer length-related change of fluorescence intensity (FAM-X-CTT-54>FAM-PEG(8)-CTT-54>FAM-CTT-54). These results suggest that selection of linkers and their lengths will be important considerations in the development of next-generation prostate tumor-targeted imaging probes and therapeutic agents that specifically home to PSMA on tumor cells. 相似文献
106.
CC van Diemen DS Postma M Siedlinski A Blokstra HA Smit HM Boezen 《Respiratory research》2011,12(1):57
Background
An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking.Methods
We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).Results
MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p = 0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.Conclusions
We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population. 相似文献107.
Berkman PJ Skarshewski A Lorenc MT Lai K Duran C Ling EY Stiller J Smits L Imelfort M Manoli S McKenzie M Kubaláková M Šimková H Batley J Fleury D Doležel J Edwards D 《Plant biotechnology journal》2011,9(7):768-775
The genome of bread wheat (Triticum aestivum) is predicted to be greater than 16 Gbp in size and consist predominantly of repetitive elements, making the sequencing and assembly of this genome a major challenge. We have reduced genome sequence complexity by isolating chromosome arm 7DS and applied second‐generation technology and appropriate algorithmic analysis to sequence and assemble low copy and genic regions of this chromosome arm. The assembly represents approximately 40% of the chromosome arm and all known 7DS genes. Comparison of the 7DS assembly with the sequenced genomes of rice (Oryza sativa) and Brachypodium distachyon identified large regions of conservation. The syntenic relationship between wheat, B. distachyon and O. sativa, along with available genetic mapping data, has been used to produce an annotated draft 7DS syntenic build, which is publicly available at http://www.wheatgenome.info . Our results suggest that the sequencing of isolated chromosome arms can provide valuable information of the gene content of wheat and is a step towards whole‐genome sequencing and variation discovery in this important crop. 相似文献
108.
Benjamin B. Kasten Tiancheng Liu Jessie R. Nedrow-Byers Paul D. Benny Clifford E. Berkman 《Bioorganic & medicinal chemistry letters》2013,23(2):565-568
Prostate-specific membrane antigen (PSMA) is a notable biomarker for diagnostic and therapeutic applications in prostate cancer. Gold nanoparticles (AuNPs) provide an attractive nanomaterial platform for combining a variety of targeting, imaging, and cytotoxic agents into a unified device for biomedical research. In this study, we present the generation and evaluation of the first AuNP system functionalized with a small molecule phosphoramidate peptidomimetic inhibitor for the targeted delivery to PSMA-expressing prostate cancer cells. The general approach involved the conjugation of streptavidin-coated AuNPs with a biotin-linked PSMA inhibitor (CTT54) to generate PSMA-targeted AuNPs. In vitro evaluations of these targeted AuNPs were conducted to determine PSMA-mediated and time-dependent binding to PSMA-positive LNCaP cells. The PSMA-targeted AuNPs exhibited significantly higher and selective binding to LNCaP cells compared to control non-targeted AuNPs, thus demonstrating the feasibility of this approach. 相似文献
109.
Kathryn Berkman Kate Haigh Ling Li Jack Lockett Goce Dimeski Anthony Russell Warrick J. Inder 《BMC endocrine disorders》2018,18(1):93
Background
Hyponatraemia is the most common electrolyte disturbance amongst hospitalised patients. Both American and European guidelines recommend fluid restriction as first line treatment for SIADH, however differ on second line recommendations. The objective of this study was to examine investigation and management of hyponatraemia in hospitalised patients in an Australian tertiary hospital.Methods
A retrospective audit was conducted of electronic medical records and laboratory data of inpatients with serum sodium (Na) ≤125?mmol/L, admitted over a 3?month period to the Princess Alexandra Hospital, Brisbane, Australia. The main outcomes measured included: demographic characteristics, investigations, accuracy of diagnosis, management strategy, change in Na and patient outcomes.Results
The working clinical diagnosis was considered accurate in only 37.5% of cases. Urine Na and osmolality were requested in 72 of 152 patients (47.4%) and in 43 of 70 euvolaemic patients (61.4%). Thyroid function tests (67.1%) and morning cortisol (45.7%) were underutilized in the euvolaemic group. In the SIADH cohort, fluid restriction resulted in a median (IQR) 7.5?mmol/L (4–10.5) increase in Na after 3?days; no treatment resulted in a median 0?mmol/L (??0.5–1.5) change. Oral urea was utilized in 5 SIADH patients where Na failed to increase with fluid restriction alone. This resulted in a median 10.5?mmol/L (3.5–13) increase in Na from baseline to day 3. There were no cases of osmotic demyelination. The median length of stay was 8?days (4–18.5). Mortality was 11.2% (17 patients). There was a weak but significant correlation between nadir serum Na and mortality (R?=?0.18, P?=?0.031).Conclusion
Inpatient hyponatraemia is often inadequately investigated, causing errors in diagnosis. Treatment is heterogeneous and often incorrect. In cases with hyponatraemia refractory to fluid restriction, oral urea presents an effective alternative treatment.110.
van Bueren KL Bennetts JS Fowles LF Berkman JL Simpson F Wicking C 《Gene expression patterns : GEP》2007,7(1-2):47-50
In a screen for genes expressed in the embryonic mouse facial primordia, we identified the gene sequence annotated as KIAA0101, which has previously been shown to encode a novel proliferating cell nuclear antigen (PCNA)-interacting protein named p15(PAF). We have since demonstrated that this protein also interacts in a complex with the tumour suppressor product p33ING1b, and that overexpression results in a decrease in UV-induced cell death. Although available data suggest widespread or ubiquitous expression in the adult, here we report highly restricted expression of the p15(PAF) gene in a spatio-temporal manner during mouse embryogenesis. Major sites of expression include the facial prominences, limbs, somites, brain, spinal cord and hair follicles. Based on the nature of its interacting partners, p15(PAF) is proposed to play a role in tumorigenesis. Our data also suggest a role in embryonic development, consistent with findings that a wide range of tumours result from aberrant activity of key developmental pathways. 相似文献