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91.
S Dedieu X Canron HR Rezvani M Bouchecareilh F Mazurier R Sinisi M Zanda M Moenner A Bikfalvi S North 《BMC medicine》2010,8(1):19
Background
Amifostine (WR-2721, delivered as Ethyol®) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. Its mechanism of action is attributed to the free radical scavenging properties of its active dephosphorylated metabolite WR-1065. However, amifostine has also been described as a potent hypoxia-mimetic compound and as a strong p53 inducer; both effects are known to potently modulate vascular endothelial growth factor (VEGF-A) expression. The angiogenic properties of this drug have not been clearly defined.Methods
Cancer cell lines and endothelial cells were used in culture and treated with Amifostine in order to study (i) the expression of angiogenesis related genes and proteins and (ii) the effects of the drug on VEGF-A induced in vitro angiogenesis.Results
We demonstrated that the treatment of several human cancer cell lines with therapeutical doses of WR-1065 led to a strong induction of different VEGF-A mRNA isoforms independently of HIF-1α. VEGF-A induction by WR-1065 depends on the activation of the eIF2alpha/ATF4 pathway. This up-regulation of VEGF-A mRNA was accompanied by an increased secretion of VEGF-A proteins fully active in stimulating vascular endothelial cells (EC). Nevertheless, direct treatment of EC with amifostine impaired their ability to respond to exogenous VEGF-A, an effect that correlated to the down-regulation of VEGFR-2 expression, to the reduction in cell surface binding of VEGF-A and to the decreased phosphorylation of the downstream p42/44 kinases.Conclusions
Taken together, our results indicate that amifostine treatment modulates tumour angiogenesis by two apparently opposite mechanisms - the increased VEGF-A expression by tumour cells and the inhibition of EC capacity to respond to VEGF-A stimulation.92.
MYRON M. KWAPISZ MD CHRISTOPH NEUHÄUSER MD STEPHAN SCHOLZ MD INGEBORG D. WELTERS MD TOBIAS LÖHR MD TILLO KOCH MD KLAUS VALESKE MD HAKAN AKINTÜRK MD JOSEF THUL MD MATTHIAS MÜLLER MD 《Paediatric anaesthesia》2009,19(9):862-871
Background: After surgical repair of congenital heart disease, inotropic support is sometimes necessary to wean from cardiopulmonary bypass. In pediatric cardiac surgery, dobutamine and dopamine are often used as inotropic support. Dopexamine is a synthetic catecholamine, which has positive inotropic and vasodilating properties. Because the hemodynamic effects of catecholamines are modified after cardiopulmonary bypass, the aim of this study was to investigate the effects of dobutamine and dopexamine on cardiac index and systemic vascular resistance index after cardiopulmonary bypass in pediatric cardiac surgery. Methods: The study was performed in a prospective, randomized, and double‐blinded cross‐over design. The investigation included 11 children for elective, noncomplex congenital heart surgery. After weaning from cardiopulmonary bypass and a 20‐min period of steady state, children received either 2.5 μg·kg?1·min?1 dobutamine or 1 μg·kg?1·min?1 dopexamine for 20 min. Cardiac index (transpulmonary thermodilution), mean arterial pressure, central venous pressure, stroke volume, systemic vascular resistance, and central venous oxygen saturation were determined. The primary outcome variable was cardiac index. Results: No difference in cardiac index was observed between the two groups (P = 0.594). Both drugs increased cardiac index, dopexamine from 3.9 ± 0.6 to 4.7 ± 0.8 l·min?1·m?2 (P = 0.003) and dobutamine from 4.1 ± 0.7 to 4.8 ± 0.7 l·min?1·m?2 (P = 0.004). During treatment with dobutamine, children presented with significantly higher mean arterial pressure (P = 0.003) and systemic vascular resistance index (P = 0.026). Conclusions: This trial demonstrates that low‐dose dobutamine and dopexamine both increase cardiac index during pediatric cardiac surgery but with different hemodynamic effects. 相似文献
93.
Coincidental hypothermia after trauma can aggravate the severity of injury and it therefore makes sense to monitor the body temperature in the preclinical setting. In a prospective study, incidence and degree of severity of hypothermia were analysed as a function of injury pattern and preclinical care. A main factor of hypothermia was severity of injury measured by the injury severity score (ISS 24.0±15.5 versus 8.3±7.8) and the revised trauma score (RTS 5.6±1.8 versus 7.3±1.1). Of the patients with multiple trauma, 88.2% were hypothermic when administered to hospital, but no reason was found concerning the rescue methods (e.g. rescue time, whole duration, weather). An increase in the rate of hypothermia was seen only after long lasting incarceration. A multivariate data analysis showed, that in addition to ISS and RTS patient age (p=0.014) was primarily responsible for hypothermia after trauma, whereas no dependency was demonstrated for other factors. Thus, parts of this analysis are in contrast with other studies. Overall approximately 50% of trauma patients in the emergency unit suffer from hypothermia, but at this time point changes in physiological control mechanisms are not yet detectable. Nevertheless prevention of hypothermia is very important in the preclinical setting. 相似文献
94.
ML Katcher P Agran D Laraque SH Pollack GA Smith HR Spivak M Tenenbein SB Tully 《Pediatrics》1999,103(2):524-526
Proper record-keeping of emergency department visits and hospitalizations of injured children is vital for appropriate patient management. Determination and documentation of the circumstances surrounding the injury event are essential. This information not only is the basis for preventive counseling, but also provides clues about how similar injuries in other youth can be avoided. The hospital records have an important secondary purpose; namely, if sufficient information about the cause and mechanism of injury is documented, it can be subsequently coded, electronically compiled, and retrieved later to provide an epidemiologic profile of the injury, the first step in prevention at the population level. To be of greatest use, hospital records should indicate the "who, what, when, where, why, and how" of the injury occurrence and whether protective equipment (eg, a seat belt) was used. The pediatrician has two important roles in this area: to document fully the injury event and to advocate the use of standardized external cause-of-injury codes, which allow such data to be compiled and analyzed. 相似文献
95.
96.
HENRIK VERDER KIRSTEN STHR JOHANSEN KRSTEN ENGBK 《Acta paediatrica (Oslo, Norway : 1992)》1973,62(1):59-65
Manometrical measurements of reflex responses in the internal anal sphincter were made in 93 patients. In normal controls, a relaxation was obtained within the internal sphincter after distension of the rectum. Patients suffering from Hirschsprung's disease showed either a contraction in the muscle or an absence of sphincteric response. In 17 cases, where the diagnosis of Hirschsprung's disease was established by conventional means, the diagnosis was confirmed by anal tonometry in 13 cases and disproved by this method in 4 cases. The subsequent clinical course and histological findings have verified the diagnosis obtained by tonometry. In one patient it was not possible to make the diagnosis by means of the usual methods, anal tonometry showed Hirschsprung's disease and this was subsequently confirmed by biopsy. 相似文献
97.
Pehlivan S Koyuncuoglu M Pehlivan M Izzetoglu S Mater Y Cabuk M Kirkali Z 《World journal of urology》2004,22(2):120-123
This study investigated the frequency of allelic imbalance (AI) in particular loci in conventional renal cell carcinoma tissue and premalignant lesions of the kidney. DNA from the tumor tissue, premalignant lesions and normal kidney tissue of radical nephrectomy specimens from 33 patients was obtained. It was amplified with a set of eight microsatellite markers, which are located on chromosomes 2, 3, 5, 8, 9, 11, 16, 17. AI in DNA samples was determined by analysis of the alteration in (CA)n repeats. The rates of AI in tumor tissue were found to be between 22.2% and 53.3% and in premalignant lesions between 11.1% and 40.0%. Premalignant lesions and tumor tissues in conventional renal cell carcinoma have the same genotypic changes in 50.0–87.8% (informative cases). These results suggest that the progressive accumulation of AI in areas of premalignant lesions may contribute to the development of renal cell carcinoma, representing an important molecular event in the multistep renal carcinogenesis cascade. 相似文献
98.
AJ Blethyn K Verrier Jones R Newcombe GM Roberts HR Jenkins 《Archives of disease in childhood》1995,73(6):532-533
A scoring system for faecal loading was constructed by two experienced observers using the abdominal radiographs of 20 children. Four other observers independently graded the radiographs using this system and there was a high degree of agreement between all six observers (p < 0.001), suggesting that radiological assessment of constipation can be standardised. 相似文献
99.
The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse 总被引:9,自引:5,他引:9
Human chromosome 15q11-q13 contains genes that are imprinted and expressed
from only one parental allele. Prader-Willi syndrome (PWS) is due to the
loss of expression of one or more paternally expressed genes on proximal
human chromosome 15q, most often by deletion or maternal uniparental
disomy. Several candidate genes and a putative imprinting centre have been
identified in the deletion region. We report that the human necdin-encoding
gene (NDN) is within the centromeric portion of the PWS deletion region,
between the two imprinted genes ZNF127 and SNRPN. Murine necdin is a
nuclear protein expressed exclusively in differentiated neurons in the
brain. Necdin is postulated to govern the permanent arrest of cell growth
of post-mitotic neurons during murine nervous system development. We have
localized the mouse locus Ndn encoding necdin to chromosome 7 in a region
of conserved synteny with human chromosome 15q11-q13, by genetic mapping in
an interspecific backcross panel. Furthermore, we demonstrate that
expression of Ndn is limited to the paternal allele in RNA from newborn
mouse brain. Expression of NDN is detected in many human tissues, with
highest levels of expression in brain and placenta. NDN is expressed
exclusively from the paternally inherited allele in human fibroblasts. Loss
of necdin gene expression may contribute to the disorder of brain
development in individuals with PWS.
相似文献
100.
Supratentorial ependymoma: CT appearance 总被引:5,自引:0,他引:5
Armington WG; Osborn AG; Cubberley DA; Harnsberger HR; Boyer R; Naidich TP; Sherry RG 《Radiology》1985,157(2):367-372
The computed tomographic appearances of 22 biopsy-proved supratentorial ependymomas were analyzed. Supratentorial ependymomas were usually intraparenchymal, larger than 4 cm, and cystic. Contrast enhancement was moderate to intense, with homogeneous or ring-enhancement patterns commonly seen. Intratumoral calcification was present in one-third of the cases, while hydrocephalus and peritumoral edema were seen in 50%. Intratumoral hemorrhage was not a characteristic of the lesion. In contrast to cellular ependymomas, malignant ependymomas and ependymoblastomas demonstrate higher attenuation prior to administration of contrast material, more intense enhancement, lower frequency of calcification within the tumor, and less distinct margination. 相似文献