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991.
Ben S Wittner Dennis C Sgroi Paula D Ryan Tako J Bruinsma Annuska M Glas Anitha Male Sonika Dahiya Karleen Habin Rene Bernards Daniel A Haber Laura J Van't Veer Sridhar Ramaswamy 《Clinical cancer research》2008,14(10):2988-2993
PURPOSE: Most node-negative breast cancer patients are older and postmenopausal and are increasingly being offered adjuvant chemotherapy despite their low overall risk of distant relapse. A molecular diagnostic test with high negative predictive value (NPV) for distant metastasis in this subgroup would spare many older breast cancer patients adjuvant treatment. EXPERIMENTAL DESIGN: We determined the NPV and positive predictive value of the MammaPrint assay in breast cancer patients who were consecutively diagnosed and treated at the Massachusetts General Hospital between 1985 and 1997. Primary tumors from 100 patients with node-negative, invasive breast cancer (median age, 62.5 years; median follow-up, 11.3 years) were subjected to MammaPrint analysis and classified as being at either low or high risk for distant metastasis. RESULTS: The MammaPrint 70-gene signature displayed excellent NPV as in previous studies, correctly identifying 100% of women at low risk for distant metastases at 5 years. However, this assay had a lower positive predictive value (12% at 5 years) than previously observed. CONCLUSIONS: The MammaPrint assay was originally designed to identify younger breast cancer patients at low risk for distant metastasis, who might consequently be spared systemic treatment. We show here that the same signature has a very high NPV for distant recurrence after adjuvant treatment in older breast cancer patients. 相似文献
992.
Bhatt DC Dhake AS Khar RK Mishra DN 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》2008,128(9):1325-1331
The transdermal matrix films of metoprolol tartrate (MT) were prepared by casting on mercury substrate employing different ratios of polymers, ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP), using dibutyl phthalate (DBT) as a plasticizer. Four formulations were prepared. Formulations MF-1, MF-2, MF-3 and MF-4 were composed of EC and PVP in the following ratios: 4.5:0.5, 4:1, 3:2 and 2:3 respectively. The formulations were subjected to various physical characterization studies namely, thickness, weight variation, drug content, moisture uptake, in vitro drug release and in vitro skin permeation. The in vitro permeation studies were carried out across excised porcine ear skin using Franz diffusion cell. Cumulative amounts of the drug released in 24 hours from the four formulations were 69.58%, 96.13%, 98.85% and 99.60%, respectively. Corresponding values for the cumulated amounts of drug permeated across the porcine skin for the above matrix films were 124.38, 153.22, 156.46 and 163.25 mug/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model (r(2)=0.9147-0.9823), and the mechanism of release was diffusion mediated. Based on the physical evaluation, in vitro drug release & permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films MF-3, composed of EC: PVP (3:2), may be suitable for the development of a transdermal drug delivery system of MT. 相似文献
993.
Natesan S Reckless GE Barlow KB Odontiadis J Nobrega JN Baker GB George SR Mamo D Kapur S 《Psychopharmacology》2008,199(2):275-289
RATIONALE: l-Stepholidine, a dopamine D(2) antagonist with D(1) agonist activity, should in theory control psychosis and treat cognitive symptoms by enhancing cortical dopamine transmission. Though several articles describe its impact on the dopamine system, it has not been systematically evaluated and compared to available antipsychotics. MATERIALS AND METHODS: We examined its in vitro interaction with dopamine D(2) and D(1) receptors and compared its in vivo pharmacokinetic profile to haloperidol (typical) and clozapine (atypical) in animal models predictive of antipsychotic activity. RESULTS: In vitro, l-stepholidine showed significant activity on dopamine receptors, and in vivo, l-stepholidine demonstrated a dose-dependent striatal receptor occupancy (RO) at D(1) and D(2) receptors (D(1) 9-77%, 0.3-30 mg/kg; D(2) 44-94%, 1-30 mg/kg), though it showed a rather rapid decline of D(2) occupancy related to its quick elimination. In tests of antipsychotic efficacy, it was effective in reducing amphetamine- and phencyclidine-induced locomotion as well as conditioned avoidance response, whereas catalepsy and prolactin elevation, the main side effects, appeared only at high D(2)RO (>80%). This preferential therapeutic profile was supported by a preferential immediate early gene (Fos) induction in the nucleus accumbens over dorsolateral striatum. We confirmed its D(1) agonism in vitro, and then using D(2) receptor, knockout mice showed that l-stepholidine shows D(1) agonism in the therapeutic dose range. CONCLUSIONS: Thus, l-stepholidine shows efficacy like an "atypical" antipsychotic in traditional animal models predictive of antipsychotic activity and shows in vitro and in vivo D(1) agonism, and, if its rapid elimination does not limit its actions, it could provide a unique therapeutic approach to schizophrenia. 相似文献
994.
Among the various mechanisms proposed, the process of non-enzymatic glycation of proteins is believed to play an important role in the pathogenesis of chronic complications associated with renal failure. The two traditional factors found to modulate the early glycation of proteins are the prevailing concentration of glucose and half life of the protein. Among the various proteins that are known to undergo nonenzymatic glycation in vivo, hemoglobin has been the most thoroughly investigated. Determination of glycated hemoglobin in diabetic patients is currently acknowledged as the most reliable indicator for assessment of retrospective glycemic control and the planning of clinical management. The clinical utility of glycated hemoglobin measurements, however, in renal failure is controversial, given the numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. With few exceptions, previous studies have suggested that the concentration of glycated hemoglobin was increased in uremic patients. There is documented evidence that increased glycated hemoglobin levels are found in certain non-diabetic states. So it stands to reason that hyperglycemia, although clearly being the culprit in diabetes, does not provide the complete answer to the etiology of increased early glycated products in non-diabetic conditions including chronic renal failure. This article reviews available evidence supporting increased glycation of hemoglobin in patients with chronic renal failure. Potential mechanisms for this increase are examined with special emphasis on the potential role of oxidative stress. 相似文献
995.
Fu DX Foss CA Nimmagadda S Ambinder RF Pomper MG 《Current pharmaceutical design》2008,14(28):3048-3065
Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications. Progress in this field continues largely due to a union between molecular genetics and advanced imaging technology. This review details uses of molecular-genetic imaging in the context of tumor-associated viruses. Under certain conditions, and particularly during pharmacologic stimulation, gammaherpesviruses will express genes that enable imaging and therapy in vivo. The techniques discussed are readily translatable to the clinic. 相似文献
996.
Two series of 10-substituted 5,5-dioxo-5,10-dihydro[1,2,4]triazolo[1,5-b][1,2,4]benzothiadiazine 2-methyl/ethyl sulfanyl benzothiazole derivatives (5a-d) and 10-substituted 5,5-dioxo-5,10-dihydro[1,2,4]triazolo[1,5-b][1,2,4] benzothiadiazine 2-phenoxy benzothiazole derivatives (16a-c) were synthesized and their structures confirmed by NMR, MS, IR and X-ray crystallography. These compounds were evaluated for their cytotoxicity against 60 human tumour cell lines. One of the synthesized compounds (5b) exhibited significant inhibitory activity against most of the cell lines and has been further evaluated for the five-dose screening. 相似文献
997.
Toxicity of Organophosphates on Morphology and Locomotor Behavior in Brine Shrimp, <Emphasis Type="Italic">Artemia salina</Emphasis> 总被引:1,自引:0,他引:1
Venkateswara Rao J Kavitha P Jakka NM Sridhar V Usman PK 《Archives of environmental contamination and toxicology》2007,53(2):227-232
The acute toxicity and hatching success of four organophosphorus insecticides—acephate (ACEP), chlorpyrifos (CPP), monocrotophos
(MCP), and profenofos (PF)—was studied in a short-term bioassay using brine shrimp, Artemia salina. Fifty percent hatchability inhibition concentration and median lethal concentration (LC50) values were calculated after probit transformation of the resulting data. Among the insecticides tested, CPP is found to
be the most toxic and also to inhibit hatching success of A. salina cysts in a concentration-dependent manner. In addition, the effect of these pesticides on locomotor behavior (swimming speed)
and morphologic differences were studied in LC50-exposed nauplii after 24 hours. The in vivo effect of these insecticides on acetylcholinesterase (Enzyme commission number (EC 3.1.1.7) activity was also determined
in LC50-exposed nauplii after 24 hours. Maximum percent decrease in their swimming speed and significant morphologic alterations
were noticed in CPP-exposed brine shrimps. The order of toxicity was CPP > PF > MCP > ACEP in all the parameters studied. 相似文献
998.
David Victor Kumar D. Krishna Chaitanya Vishram Singh D. Sridhar Reddy 《Journal of the Anatomical Society of India》2018,67(1):12-17
Introduction
Malleus, Incus and Stapes are the three middle ear ossicles which form an articulated chain and help in conduction of sound from external ear to inner ear. Morphometric study of these ossicles has been going since the early 60s. Although the methods of been changing due to advent of newer technologies and treatments.Methods
We studied ossicles of 60 temporal bones. The ossicles have been obtained by ‘canal-wall down’ mastoidectomy technique. They have been measured by an open software, Fiji (https://imagej.nih.gov) where the scale was standardized and set to mm (millimeter).Results
The mean total length of the malleus is 8.23 mm; a mean angle of 128.76°, mean width of the head 2.56 mm, and mean length of manubrium is 4.17 mm. The mean total length of incus is 7.04 mm, mean angle of 97.23°, mean total width of 5.31 mm, and mean length of long process is 3.27 mm. The mean total height of stapes is 3.44 mm; mean width of the footplate is 1.10 mm and a mean angle of 51.01°.Discussion
Morphometric data obtained in the present study can be useful for the reconstructive procedures. Preoperative radiological assessment is advised for these small bones. The present study also emphasizes on the future directions where in reconstructive procedures can be improved with the artistic renderings of the blueprints provided, for new prosthetic designs which can be manufactured by using Teflon materials. 相似文献999.
Vishram Singh D. Krishna Chaitanya Reddy David Victor Kumar I. B.K.S. Chauhan Sridhar Reddy 《Journal of the Anatomical Society of India》2018,67(2):110-114
Introduction
Facial nerve (C.N VII) is the nerve of facial expression and communication. The intratemporal part of this nerve comprising tympanic and mastoid segments, is very vulnerable to injury during ear surgeries. Hence to safely navigate around this part of the nerve one has to be very familiar with 3D anatomy of the temporal bone and crucial landmarks present in relation to the nerve. Aim of this study is to know the exact morphometry of Intratemporal part of the facial nerve in relation to Pneumatization of temporal bone.Material and methods
The present study was carried out on 54 cadaveric temporal bones obtained from the department of anatomy, Santosh Medical College, Santosh University, Delhi-NCR. With the pneumatization determined by computerized tomography (CT), the dissection was performed by standard techniques of ‘canal wall up’ mastoidectomy and ‘canal wall down’ mastoidectomy. Temporal bones have been classified into 3 groups: Group I-Well Pneumatised bones, Group II- Mixed type of Pneumatised bones and Group III- Sclerosed bones. The mean, standard deviation (S.D), maximum and minimum values were calculated in all the groups for the lengths of the facial nerve.Results
The total length of the intratemporal part of facial nerve ranged between 19.71–30.13 mm for group I, 21.77–27.27 mm in group II and 16.21–25.19 mm in group III respectively.Discussion
The distal segment of nerve is most commonly injured during otologic surgeries. Incus pointer can be considered as a landmark to identify the facial nerve. Accordingly the tympano mastoid part of the facial nerve can be divided into proximal, distal and stylomastoid foramen segments. Radiological evaluations such as Computed Tomographic (CT) imaging techniques and MRI techniques like FIESTA (Fast Imaging Employing Steady-state Acquisition) have become popular in identifying these segments. The morphometric values of facial nerve provided in the present study can help in assessment during procedures, like end to end anastamosis and cable nerve graft repairs in iatrogenic injuries. 相似文献1000.
Gautomi Gogoi Labanya Bhattacharya Smruti R. Sahoo Sridhar Sahu Neelotpal Sen Sarma Sagar Sharma 《RSC advances》2020,11(1):57
In this study, the impact of fluoroalkyl side chain substitution on the air-stability, π-stacking ability, and charge transport properties of the versatile acceptor moiety naphthalene tetracarboxylic diimide (NDI) has been explored. A density functional theory (DFT) study has been carried out for a series of 24 compounds having different side chains (alkyl, fluoroalkyl) through the imide nitrogen position of NDI moiety. The fluoroalkyl side chain engineered NDI compounds have much deeper highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) than those of their alkyl substituted compounds due to the electron withdrawing nature of fluoroalkyl groups. The higher electron affinity (EA > 2.8 eV) and low-lying LUMO levels (<−4.00 eV) for fluoroalkyl substituted NDIs reveal that they may exhibit better air-stability with superior n-type character. The computed optical absorption spectra (∼386 nm) for all the investigated NDIs using time-dependent DFT (TD-DFT) lie in the ultra-violet (UV) region of the solar spectrum. In addition, the low value of the LOLIPOP (Localized Orbital Locator Integrated Pi Over Plane) index for fluoroalkyl side chain comprising NDI compounds indicates better π–π stacking ability. This is also in good agreement for the predicted π–π stacking interaction obtained from a molecular electrostatic potential energy surface (ESP) study. The π–π stacking is thought to be of cofacial interaction for the fluoroalkyl substituted compounds and herringbone interaction for the alkyl substituted compounds. The calculated results shed light on why side chain engineering with fluoroalkyl groups can effectively lead to better air-stability, π-stacking ability and improved charge transport properties.In this study, the impact of fluoroalkyl side chain substitution on the air-stability, π-stacking ability, and charge transport properties of the versatile acceptor moiety naphthalene tetracarboxylic diimide (NDI) has been explored. 相似文献