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1.
Sintov Amnon Scott William A. Gallagher Kim P. Levy Robert J. 《Pharmaceutical research》1990,7(1):28-33
Epicardial antiarrhythmic drug administration was studied as a therapeutic approach for experimental ventricular tachycardia (VT) in an open-chest dog model. Lidocaine-polyurethane matrices (28%, w/w) were formulated as a model system. Matrices were placed on the left ventricular epicardium in each of 23 anesthetized open-chest dogs with ouabain-induced VT, to evaluate effectiveness in restoring sinus rhythm. Conversion occurred in all animals treated with matrices containing 300 mg or more of lidocaine after 1.5 to 7.0 min. The matrix lidocaine content correlated linearly with the time required for conversion to sinus rhythm (r = 0.75, P = 0.0002); irrespective of matrix size the myocardial/plasma lidocaine ratio was 20.1 ± 4.2 (mean ± SD) at the time of conversion. In a separate series of five dogs without ventricular tachycardia, systolic wall thickening measured with sonomicrometers after 5 min of controlled-release lidocaine administration (500- to 1000-mg matrix lidocaine content, 7.48 ± 3.49-mg/kg dose) was only minimally diminished (–14.1%) and this effect was observed only at the site of matrix placement on the anterior-apical epicardium. In contrast, intracoronary injection of 0.3 or 1.0 mg/kg of lidocaine-HCl resulted in complete elimination of wall thickening or replacement by systolic thinning. Thus epicardial administration of lidocaine from polyurethane matrices was an effective means of treating ouabain-induced ventricular tachycardia. Regional myocardial function in the vicinity of the matrices was modified to a very limited degree, supporting the view that the matrices can be used safely, without serious risk to ventricular contractile performance. 相似文献
2.
Oleg Dukhno M.D. Jochanan Peiser M.D. M.P.H. Isaac Levy M.D. F.A.C.S. Amnon Ovnat M.D. 《Surgery for obesity and related diseases》2006,2(1):S39-63
A patient developed a huge diaphragmatic hernia following laparoscopic gastric banding. Almost the entire stomach was incarcerated within the left chest. Segmental necrosis of the greater curvature of the stomach necessitated partial gastrectomy. The postoperative course was uneventful. The etiology, diagnosis and treatment of this previously undescribed complication of laparoscopic gastric banding are addressed in relation to the present case. 相似文献
3.
The apparent concentration-effect relationship is the ensemble of many effector units (such as individual cells or channels)
that do not always exhibit a uniform stimulus-effect relationship. This concept is substantiated by many observations of heterogeneity
in receptor-effector populations including hormone secreting cells, response to hormonal stimuli, activity pattern of second
messengers, stimulus-evoked synaptic currents, and single ion channels. The relationship between drug concentration and magnitude
of pharmacologic response is commonly described by the sigmoidalE
max model which was derived from the Hill equation. The sigmoidicity factor (N) in this model is assumed to be a pure mathematical parameter without physiological connotations. This work demonstrates
that the numerical value ofN (measured empirically) is the product of two factors: (i) the degree of heterogeneity of the effector subunits, i.e., the
elemental component that upon drug stimulus contributes its pharmacological effect independently and does not interact with
other subunits (it could range from a single receptor up to a whole tissue), and (ii) value ofN
*—the shape factor of the subunits' concentration-effect relationship. A special case of this approach occurs whenN
*>5, which is an on-off case. HereN is determined by the distribution (density equation) of the subunit values. In case of heterogeneity of the microparameters
of the effector subunits the apparentN will always have a lower value thanN
*. According to this theory it can be concluded that without knowledge of the distribution of the microparameters no mechanistic
interpretation can be deduced from the apparentN value. If in the futureN
* can be determined by theoretical or experimental methods, the distribution function relatingN
* toN can be calculated. The relevance of this theory is increased in view of the progress being made in advanced research techniques
which may enable us to determine the concentration-effect relationship at the level of the individual effector unit. 相似文献
4.
Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content 总被引:4,自引:0,他引:4
Pharmaceutical Research - 相似文献
5.
6.
Takebumi Onda Drake Laface Gottfried Baier Thomas Brunner Nakayuki Honma Toshifumi Mikayama Amnon Altman Douglas R. Green 《Molecular immunology》1995,32(17-18)
The process of T cell recognition involves a complex set of interactions between the various components of the TCR/MHC/peptide trimolecular complex. We have developed a system for exploring the specific binding interactions contributed by the constituent subunits of TCR complexes for components of their ligands. We utilized an M13 phage display system, designed for multivalent receptor display, to explore specific binding interactions between various TCRα chains and specific antigen in the absence of MHC. The multivalent TCR-phage display system was sensitive enough to reveal some TCRα chains capable of binding directly to antigen with the same fine specificity shown by the MHC-restricted T cells from which the α chains were derived. Cross-specificity analysis using two antigen-binding TCRα chains derived from T cells with different polypeptide antigen specificities confirmed the fidelity of this binding. In mixtures of antigen-binding and non-binding TCRα-displaying phage, specific selection was achieved at a starting frequency of 1/1000, suggesting that this system can be employed for selection and analysis of TCR-displaying phage libraries. While the binding specificities exhibited by these TCRs are unusual, they provide a novel perspective from which to study the specific binding interactions that constitute TCR antigen binding. 相似文献
7.
Mark A. Rabinovitch Victor Kalff Richard Allen Amnon Rosenthal James Albers Sunil K. Das Bertram Pitt Dennis P. Swanson Thomas Mangner W. Leslie Rogers James H. Thral William H. Beierwaltes 《European journal of nuclear medicine and molecular imaging》1985,10(5-6):222-227
The utility of -123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40° LAO projection after a standard dose of -123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients.Of the 16 patients, only 2 had distinctly abnormal -123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which cartine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, -123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.Supported by a Canadian Heart Foundation Research FellowshipSupported by an Australian Heart Foundation Travel Grant 相似文献
8.
The purpose of this investigation was to determine whether paraplegia induced by neoplastic cord compression affects the pharmacodynamics of phenobarbital general anesthesia or of pentylenetet-razol (PTZ)-induced convulsions. Paraplegic rats harboring a thora-columbar epidural tumor, or an identical hindlimb tumor mass, received an i.v. infusion of phenobarbital until the onset of anesthesia. At that point, the phenobarbital concentrations in the CSF and serum were measured. Similarly, PTZ was infused until the onset of maximal seizures. It was found that changes related to systemic tumor growth and newly developed paraplegia due to neoplastic spinal cord compression did not attenuate the pharmacodynamics of phenobarbital. However, sustained paraplegia of 4 days duration reduced CNS sensitivity to the hypnotic action of the barbiturate as evidenced by the higher cerebrospinal fluid phenobarbital concentration required to induce anesthesia (170 ± 31 vs 125 ± 20 mg/L; P < 0.05). On the other hand, sustained paraplegia did not affect brain threshold concentration for PTZ-induced seizures. 相似文献
9.
Michael Cohen Ruby Ann Small Amnon Brzezinski 《Breast cancer research and treatment》1995,33(3):257-264
Summary The use of the conventional combination oral contraceptives (containing ethinyl-estradiol and a progestin) is associated with reduced risk of ovarian and endometrial cancer. However, prolonged use of these pills before first term pregnancy apparently increases the risk of pre menopausal breast cancer. We propose that the pineal gland hormone melatonin, combined with a progestin, as a new and novel oral contraceptive combination might prevent breast cancer in long term users. This hypothesis is based on the assumption that women have a propensity to develop breast cancer which correlates with number of ovulatory cycles over their lifetime. In evolution, the phylogenetic point at which women became sensitive to breast cancer evolved at a transfer point of the mechanism of ovulation from seasonal ovulation, which is still common in many mammalian species, to the current human pattern of continuous ovulatory cycles. We suggest that melatonin/ovariansteroid contraceptive will restore the lost mechanism of endogenous anovulation, and thus, by preventing continuous epithelial breast cell proliferation, will reduce the risk of breast cancer in long-term users. 相似文献
10.
Amnon Zung Yardena Tenenbaum‐Rakover Shiri Barkan Aaron Hanukoglu Eli Hershkovitz Orit Pinhas‐Hamiel Tzvy Bistritzer Zvi Zadik 《Clinical endocrinology》2010,72(2):264-271
Introduction Neonatal hyperthyrotropinaemia (HT), defined by elevated TSH and normal T4, is either transient or persistent. The eventual outcome of neonatal HT is unpredictable and the management of HT patients is controversial. We assessed perinatal parameters and diagnostic measures that may distinguish between transient and persistent HT, compared with congenital hypothyroidism (CH). We also aimed to recommend optimal treatment in these forms of thyroid impairment. Design and patients A multi‐centre, retrospective study was conducted in six paediatric endocrinology units. Forty‐three HT patients and 83 CH patients were included in the study. Measurements We evaluated differences in birth weight (BW), gestational age (GA), modes of diagnosis, screening and confirmatory T4 and TSH levels, thyroid imaging results and optimal thyroxine doses between HT and CH and between the two forms of HT. Results Newborns with HT had lower BW and GA than those with CH. Transient (n = 18) and persistent HT (n = 25) patients were indistinguishable by most parameters, but those with persistent HT had a higher prevalence of abnormal thyroid imaging (69%vs 8%; P = 0·005). During treatment, 79% and 55% of transient and persistent HT patients respectively experienced elevated levels of free T4. Although most HT patients were reevaluated after 2·5 years, six transient HT patients stopped therapy and showed full recovery within the first year of life. Conclusions We recommend obtaining thyroid imaging to distinguish between the two forms of HT. Adherence to recommended doses of thyroxine and probably early cessation of therapy in transient HT can prevent iatrogenic hyperthyroidism in these patients. 相似文献