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排序方式: 共有386条查询结果,搜索用时 15 毫秒
101.
Martins PS Brunialti MK Martos LS Machado FR Assunçao MS Blecher S Salomao R 《Critical care (London, England)》2008,12(1):R25
Background
Infection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. The aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction. 相似文献102.
Increased blood pressure and left ventricular (LV) mass predict the onset of the clinically manifest hypertension, but little is known regarding the possible predictive value of LV function. The present study was designed to evaluate the association between echocardiographic LV long-axis systolic, and diastolic function and hypertension onset. We prospectively followed 244 normotensive adults with a family history of hypertension (HTN), with echocardiography for 7 years. M-mode derived atrioventricular plane displacement of the mitral and tricuspid annuli (MAVPD and TAVPD respectively), and LV circumferential fractional shortening were calculated. Diastolic function of the left and right ventricle were assessed using Doppler indices of the mitral and tricuspid inflow. During follow-up, 79 subjects developed hypertension (H group) and 165 subjects remained normotensive (N group). H group subjects had diminished MAVPD (13.8+/-3.4 vs 15.0+/-3.1 mm; P=0.007), lower mitral E/A ratio, and longer mitral E-wave deceleration time as compared to N group. In multivariate Cox model MAVPD and mitral E/A ratio predicted the onset of hypertension independent of LV mass index, blood pressure, pre-hypertensive status at baseline, age, sex and body mass index. During follow-up, H subjects experienced a significant decline in MAVPD and mitral E/A ratio, whereas the indices of right ventricular function and LV circumferential shortening remained intact. In conclusion, alterations in LV long-axis systolic and diastolic function, as measured by MAVPD and E/A ratio predict the onset of hypertension. These parameters declined during the development of hypertension. 相似文献
103.
104.
S Slater MJ Crawford MA Kabbouche SL LeCates S Cherney P Vaughan A Segers P Manning D Burdine SW Powers & AD Hershey 《Cephalalgia : an international journal of headache》2009,29(9):969-973
The aim of this study was to evaluate the impact of gender and age on headache characteristics and disability. Headache characteristics were assessed at an initial visit to a paediatric specialty care centre and five follow-up visits. A total number of 4121 patients were evaluated. Fifty-eight per cent of the sample was female. Boys were younger at their first headache and initial visit. They more frequently described headache pain as squeezing and location as top of the head. Girls reported more frequent and longer headaches. Girls more often described headache pain as sharp and location as back of the head. Age accounted for more variance than gender in headache severity, duration, frequency and disability. Gender differences exist in headache characteristics. Age is also an important factor in the variability in characteristics and disability. Longitudinal studies are needed to describe further the natural history of headaches in childhood and compare outcome between genders. 相似文献
105.
Cohen MC Curran PJ L'Italien GJ Mittleman MA Zarich SW 《The American journal of cardiology》1999,83(7):1038-1042
The objective of this study is to assess the prognostic impact of preoperative dipyridamole thallium imaging and clinical variables on the long-term outcome of diabetic patients undergoing peripheral vascular surgery. Complete follow-up was obtained in 101 consecutive patients with diabetes mellitus undergoing routine dipyridamole thallium scintigraphy before vascular surgery (mean 4.2 +/- 3.2 years, range 1 month to 11 years). Low risk was defined by diabetes alone with a normal resting electrocardiogram. High risk was defined as a history of angina, myocardial infarction, congestive heart failure, or resting electrocardiogram abnormalities. There were 71 deaths in 98 patients discharged alive from the hospital (median survival 4.4 years). Age, the presence of resting electrocardiogram abnormalities, and an abnormal thallium scan were independent predictors of late death. After adjusting for age >70 years and thallium abnormalities, high-risk patients had a death rate 4.8 times (95% confidence interval 1.7 to 13.4, p <0.002) greater than low-risk patients. The presence of >2 reversible thallium defects was useful in further risk stratification of both low- and high-risk patients. Low-risk patients with >2 reversible defects had a median survival of 4.0 years compared with 9.4 years in those with < or =2 reversible defects (p <0.001). Similarly, high-risk patients with < or =2 reversible defects had an intermediate median survival rate of 4.7 years compared with 1.8 years in the group with >2 reversible defects (p <0.001). Therefore, advanced age and the presence of resting electrocardiographic or thallium abnormalities identifies a subset of diabetic patients with a poor long-term outcome after vascular surgery. Combined clinical and thallium variables may identify a population in whom intensive medical or surgical interventions may be warranted to reduce both perioperative and late cardiac events. 相似文献
106.
Miller R Ewy W Corrigan BW Ouellet D Hermann D Kowalski KG Lockwood P Koup JR Donevan S El-Kattan A Li CS Werth JL Feltner DE Lalonde RL 《Journal of pharmacokinetics and pharmacodynamics》2005,32(2):185-197
The idea of model-based drug development championed by Lewis Sheiner, in which pharmacostatistical models of drug efficacy
and safety are developed from preclinical and available clinical data, offers a quantitative approach to improving drug development
and development decision-making. Examples are presented that support this paradigm. The first example describes a preclinical
model of behavioral activity to predict potency and time-course of response in humans and assess the potential for differentiation
between compounds. This example illustrates how modeling procedures expounded by Lewis Sheiner provided the means to differentiate
potency and the lag time between drug exposure and response and allow for rapid decision making and dose selection. The second
example involves planning a Phase 2a dose-ranging and proof of concept trial in Alzheimer’s disease (AD). The issue was how
to proceed with the study and what criteria to use for a go/no go decision. The combined knowledge of AD disease progression,
and preclinical and clinical information about the drug were used to simulate various clinical trial scenarios to identify
an efficient and effective Phase 2 study. A design was selected and carried out resulting in a number of important learning
experiences as well as extensive financial savings. The motivation for this case in point was the “Learn-Confirm” paradigm
described by Lewis Sheiner. The final example describes the use of Pharmacokinetic and Pharmacodynamic (PK/PD) modeling and
simulation to confirm efficacy across doses. In the New Drug Application for gabapentin, data from two adequate and well-controlled
clinical trials was submitted to the Food and Drug Administration (FDA) in support of the approval of the indication for the
treatment of post-herpetic neuralgia. The clinical trial data was not replicated for each of the sought dose levels in the
drug application presenting a regulatory dilemma. Exposure response analysis submitted in the New Drug Application was applied
to confirm the evidence of efficacy across these dose levels. Modeling and simulation analyses showed that the two studies
corroborate each other with respect to the pain relief profiles. The use of PK/PD information confirmed evidence of efficacy
across the three studied doses, eliminating the need for additional clinical trials and thus supporting the approval of the
product. It can be speculated that the work by Lewis Sheiner reflected in the FDA document titled “Innovation or Stagnation:
Challenge and Opportunity on the Critical Path to New Medical Products” made this scientific approach to the drug approval
process possible. 相似文献
107.
Carcinogenic polycyclic aromatic hydrocarbons increase intracellular Ca2+ and cell proliferation in primary human mammary epithelial cells 总被引:1,自引:1,他引:1
Previous studies have shown that polycyclic aromatic hydrocarbons (PAHs)
mobilize intracellular Ca2+ in human T cells by inositol
trisphosphate-dependent mechanisms resulting from activation of
phospholipase C-gamma by SRC-related protein tyrosine kinases, thereby
mimicking antigen-receptor activation. Ca2+ appears to play an important
second messenger role in growth factor control of cell proliferation in
human mammary epithelial cells (HMEC), such as the epidermal growth factor
receptor pathway. The purpose of the present studies was to determine if
PAHs are able to increase intracellular Ca2+ in primary cultures of HMEC
and increase cell proliferation. Two carcinogenic and two non-carcinogenic
PAHs were tested for their ability to increase intracellular Ca2+ in HMEC.
The carcinogenic PAHs dimethylbenz[a]anthracene (DMBA) and benzo[a] pyrene
(BaP) were able to cause Ca2+ elevation in HMEC at early time points (2 h)
and caused sustained alterations in Ca2+ homeostasis (18 h). DMBA showed
maximal effects at early time points (2 h), while BaP showed maximal
effects on sustained Ca2+ (18 h). 2,3,7,8-Tetrachlorodibenzo-p-dioxin
(TCDD), a potent dioxin and tumor promoter, produced maximal Ca2+ elevation
at 2 h, with a return to near baseline levels by 6 h. The non-carcinogenic
PAHs benzo[e]pyrene and anthracene did not significantly alter
intracellular Ca2+ at any time point. alpha-Naphthoflavone significantly
reduced the Ca2+ response induced by BaP treatment, but not by DMBA or
TCDD, suggesting that P450 1A or 1B metabolism of BaP may be important in
the sustained Ca2+ elevating response. In evaluating the effects of BaP on
HMEC proliferation, BaP was found to increase the number of cells recovered
after 4 days in culture in the absence or presence of various
concentrations of epidermal growth factor. These studies provide initial
evidence that Ca2+ signaling may be associated with mitogenesis in HMEC,
which may play a role in tumor promotion and progression produced by PAHs.
相似文献
108.
Three cases of asymptomatic intussusception in adults are reported, discovered incidentally during a CT scan of the abdomen. It is being increasingly observed in adults, possibly aided by the reformatting capabilities of the new multislice CT scanners. It has been documented in children where it is considered to be transient and of no clinical significance. 相似文献
109.
Roessler E; Belloni E; Gaudenz K; Vargas F; Scherer SW; Tsui LC; Muenke M 《Human molecular genetics》1997,6(11):1847-1853
Holoprosencephaly (HPE) is the most common brain anomaly in humans,
involving abnormal formation and septation of the developing central
nervous system. Among the heterogeneous causes of HPE, mutations in the
Sonic Hedgehog (SHH) gene have been shown to result in an autosomal
dominant form of the disorder. Here we describe a total of five different
mutations in the processing domain encoded by exon 3 of SHH in familial and
sporadic HPE. This is the first instance in humans where SHH mutations in
the domain responsible for autocatalytic cleavage and cholesterol
modification of the N-terminal signaling domain of the protein have been
observed.
相似文献
110.