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21.
By synthesizing and testing a part-structure, N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3), derived from our previously reported high affinity sigma receptor ligands (1S,2R)-(-)-N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1- pyrrolidinyl)cyclohexylamine [(-)-2] and (+)-2, we have identified a novel class of superpotent (subnanomolar affinity) sigma ligands specific for the sigma receptor labeled by [3H]-(+)-3-PPP. When 3 was tested for its capacity to displace [3H]-(+)-3-PPP from guinea pig brain membranes, it exhibited a Ki of 0.34 nM, which is better than either of its parent compounds (-)-2 (Ki = 1.3 nM) and (+)-2 (Ki = 6.0 nM). Other compounds related to 3 such as N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-homopiperidinyl)ethy lamine (19) exhibited Ki = 0.17 nM [( 3H]-(+)-3-PPP). The determinants for high sigma receptor affinity of 3 were examined by manipulation of this structure in a number of different ways. The high efficacy of these compounds for the sigma receptor, their relative chemical simplicity and ease of synthesis, and their high degree of selective identifies N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) and related compounds as a highly promising base for determination of the functional role of sigma receptors as well as the development of novel therapeutic agents. 相似文献
22.
S Falcone R M Quencer B Bowen J H Bruce T P Naidich 《AJNR. American journal of neuroradiology》1992,13(1):403-406
The authors present two biopsy-proved cases of Creutzfeldt-Jakob disease. MR appears to be more sensitive than CT in detecting pathologic changes; signal abnormalities, when found, are predominantly within gray matter and may involve only peripheral cortex. 相似文献
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P E Bowen S Mobarhan C Henderson M Stacewicz-Sapuntzakis H Friedman R Kaiser 《JPEN. Journal of parenteral and enteral nutrition》1988,12(5):484-489
We have found that 12 patients requiring permanent enteral feeding secondary to cerebrovascular accident with adequate Vitamin A nutritional status had serum concentrations of various carotenoids which were only 8-17% of sex- and age-matched healthy controls. Their serum retinol levels were normal, but only 61% of their controls despite receiving two to three times the recommended daily allowance (RDA) in retinol equivalents. Commercial enteral formulas were found to contain only negligible quantities of the carotenoids and were the cause of the hypocarotenemia. To assess the ability of these patients to absorb beta-carotene, nine tube-fed patients were given 15 mg of beta-carotene (2.5 times the RDA) in a single dose. Serum concentration time curves showed that only four patients absorbed significant quantities of the beta-carotene and absorption was delayed compared to previously studied subjects taking enteral formulas as meals. These studies suggest that the efficiency of absorption of the fat soluble vitamins may be lower in tube-fed patients and that patients receiving long-term tube feeding are denied the possible protective effects of the carotenoids normally contained in the American diet. 相似文献
25.
26.
A.M. Vacca-Smith B.C. Van Wuyckhuyse L.A. Tabak W.H. Bowen 《Archives of oral biology》1994,39(12):1063-1069
Experiments sought to determine the nature of the binding of milk proteins to hydroxyapatite (HA) and to saliva-coated hydroxyapatite (sHA), and to determine the effect of milk and casein on the adherence of Streptococcus mutans GS-5 to sHA. The binding of radiolabelled -casein to HA was reduced when incubated simultaneously with parotid saliva, and enhanced in the presence of milk. The binding of β- and κ-casein to HA was unaffected by the presence of parotid saliva and enhanced by the presence of milk. The in vitro bacterial adherence of Strep. mutans GS-5 to sHA beads was reduced when beads were coated with milk instead of buffer, or when bacteria were added to sHA in the presence of milk instead of buffer. Casein proteins (, β, κ) added to sHA simultaneously with bacteria inhibited the adherence of Strep. mutans GS-5 to sHA. κ-Casein, when bound to sHA, inhibited streptococcal adherence to sHA; - and β-casein, when bound to sHA, had no effect on streptococcal adherence. Fractionation of κ-casein by anion-exchange chromatography revealed the anti-adherence activity of κ-casein was mediated primarily by a 40,000 mol. wt. glycoprotein-containing fraction. These data show that milk, particularly κ-casein fractions, can modulate the adherence of Strep. mutans GS-5 to SHA surfaces in vitro. 相似文献
27.
Cherri Hobgood MD Susan Sawning MSW Josie Bowen MD Katherine Savage MA 《Academic emergency medicine》2006,13(12):1288-1295
The disparities in health care and health outcomes between the majority population and cultural and racial minorities in the United States are a problem that likely is influenced by the lack of culturally competent care. Emergency medicine and other primary-care specialties remain on the front lines of this struggle because of the nature of their open-door practice. To provide culturally appropriate care, health care providers must recognize the factors impeding cultural awareness, seek to understand the biases and traditions in medical education potentially fueling this phenomenon, and create a health care community that is open to individuals' otherness, thus leading to better communication of ideas and information between patients and their health care providers. This article highlights the rationale for and current problems in teaching cultural competency and examines several different models implemented to teach and promote cultural competency along the continuum of emergency medicine learners. However, the literature addressing the true efficacy of such programs in leading to long-lasting change and improvement in minority patients' clinical outcomes remains insufficient. 相似文献
28.
The purpose of this study is to develop a new vascularized epiphyseal plate model in the New Zealand White rabbit using a metatarsal epiphyseal plate having limited longitudinal growth potential. Such a model could be utilized in various experiments aimed at manipulating epiphyseal plate growth. The viability of the harvested live subject grafts was demonstrated with continued epiphyseal uptake during Tc99-MDP radionuclide bone scanning. The currently described models used in epiphyseal transplant research all involve long bone epiphyseal plates with significantly greater growth potential than the new metatarsal model. This new model therefore fills a void in the field by allowing investigators to transplant a growth plate with limited growth potential into any heterotopic site and study the effects of various hormonal and physical influences upon epiphyseal plate growth performance. © 1995 Wiley-Liss, Inc. 相似文献
29.
P S Charifson J P Bowen S D Wyrick A J Hoffman M Cory A T McPhail R B Mailman 《Journal of medicinal chemistry》1989,32(9):2050-2058
Conformational studies on a series of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines that possess an identical substituent pattern to the prototypical D1 dopamine receptor antagonist SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (1)] were performed with use of molecular mechanics calculations [MM2(85), with newly developed aromatic halide bending and torsional parameters that are now incorporated into MM2(87)], single-crystal X-ray analysis, and high-field NMR spectroscopy. The synthesis and biological testing of compounds 2-7 has been previously reported. The test compounds were compared both quantitatively and graphically to compound 1. Calculations on both the free-base and protonated forms of each compound were carried out. To insure that conformation space was adequately sampled, the test compounds were energy minimized from different starting geometries; ring inversion of the heterocycle was employed, as were dihedral driver calculations on the phenyl or benzyl rings. For N-methyl-6-chloro-7-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (2), it was determined that the torsion angle tau(C8a-C1-C12-C17) had energy minima at approximately 60 degrees and 240 degrees. This finding was corroborated by NMR studies that indicated a dramatic upfield chemical shift of ArH8 after ring cyclization. The nitrogen lone pair or hydrogen vector was approximately orthogonal to the plane of the substituted aromatic ring in the tetrahydroisoquinolines; this explained the upfield chemical shift of the vicinal chiral proton (H1). In all instances, the 6-membered heterocyclic ring in the energy-minimized structures preferred the half-chair conformation with the phenyl rings pseudo-equatorial. Distance comparisons of the proposed pharmacophoric atoms (Cl, N, O, centroid of the phenyl or benzyl ring) showed that the phenyl or benzyl centroid to ammonium H distance, Cl to N distance, and distance of the nitrogen above or below the plane of the isoquinoline aromatic ring are the distances most highly correlated with biological activity (r = 0.82, 0.75, 0.81, respectively). Resolution and single-crystal X-ray analysis of compound 2 showed the most active enantiomer to possess the S absolute configuration, in contrast to the benzazepine (R)-1. Least-squares fitting of the energy-minimized structures with SYBYL molecular modeling software showed (S)-(+)-2, rather than (R)-(-)-2, gave a better fit to (R)-1. Volume determinations derived from SYBYL multifit analyses aided in receptor mapping to qualitatively describe areas of "active" pharmacophore space as well as areas of "inactive" substituent space.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
30.