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11.
Christian Foged Christer Halldin Christian Loc’h Bernard Mazière Stefan Pauli Mariannick Maziére Holger C. Hansen Tetsuya Suhara Carl-Gunnar Swahn Per Karlsson Lars Farde 《European journal of nuclear medicine and molecular imaging》1997,24(10):1261-1267
NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand
for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241.
This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised
by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake
of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after
injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with
flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection.
The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands
for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.
Received 19 April and in revised form 10 June 1997 相似文献
12.
Fredrik Ghosh Karl Engelsberg Robert V. English Robert M. Petters 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2007,245(6):835-846
Background The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa
and to establish graft development, long-term survival, graft-host integration, and effects on the host retina.
Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal
space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with
immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months.
Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal
connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods
in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference
in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly
from 4 to 6 months while the rod response in control eyes decreased significantly.
Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part,
the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do
not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated
graft counteracts this effect and rescues rods from degeneration.
Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The
Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New
Technologies for the Blind. 相似文献
13.
Per Karlsson Lars Farde Christer Halldin Carl-Gunnar Swahn Göran Sedvall Christian Foged Kristian Tage Hansen Birte Skrumsager 《Psychopharmacology》1993,113(2):149-156
The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with11C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D1-dopamine receptors. This striatal uptake was displaced by high doses of the selective D1-antagonist SCH 23390 (2 mg/kg) but not by the 5HT2-antagonist ketanserin (1.5 mg/kg) or the selective D2-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [11C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [11C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [11C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [11C]NNC 756 the ratio was about 5. This ratio of 5 for [11C]NNC 756 is the highest obtained so far for PET radioligands for the D1-dopamine receptor. 相似文献
14.
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16.
Christer Betsholtz Monica Nistér Fredrik Rorsman Carl-Henrik Heldin Bengt Westermark 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1989,10(1):27-36
The platelet-derived growth factor (PDGF) family consists of three different dimeric forms, AA, BB, and AB, of the two consitituent polypeptide chains, A and B. These interact with two different cell surface receptors that, in part, mediate different cellular functions. The various forms of PDGF, as well as the receptors, are expressed at high frequency in glioblastoma multiforme, and it has been suggested that the growth of this tumor might be affected by autocrine loops involving PDGF and its receptors. The present paper focuses on recent discoveries regarding the family of PDGF ligands and receptors, as well as reviews results concerning PDGF-dependent autocrine growth in experimental and spontaneous glioblastoma. 相似文献
17.
Fredrik Mertens Auxilium Albert Sverre Heim Johan Lindholm Otte Brosj Felix Mitelman Nils Mandahl 《Genes, chromosomes & cancer》1994,11(4):271-272
Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22), add(12)(p13)/46,idem,t(3;8)(p21;q13),add(10)(q26),der(15)del(15)(q15q22)ins(15;?)(q15;?)/46,idem,-X, + 2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations. 相似文献
18.
Renal sodium transport and oxygen consumption 总被引:5,自引:0,他引:5
Kiil Fredrik; Aukland Knut; Refsum Harald E. 《The American journal of physiology》1961,201(3):511-516
19.
Pettersson F Vogt AM Jonsson C Mok BW Shamaei-Tousi A Bergström S Chen Q Wahlgren M 《Infection and immunity》2005,73(11):7736-7746
The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99mtechnetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal. iRBC of different lines and clones sequester avidly in vivo while uninfected erythrocytes did not. Histological examination revealed that a multiadhesive parasite adhered in the larger microvasculature, inducing extensive intravascular changes while CD36- and chondroitin sulfate A-specific parasites predominantly sequester in capillaries, inducing no or minor pathology. Removal of the adhesive ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), preincubation of the iRBC with sera to PfEMP1 or preincubation with soluble PfEMP1-receptors prior to injection significantly reduced the sequestration. The specificity of iRBC binding to the heterologous murine receptors was confirmed in vitro, using primary rat lung endothelial cells and rat lung cryosections. In offering flow dynamics, nonmanipulated endothelial cells, and an intact immune system, we believe this syngeneic animal model to be an important complement to existing in vitro systems for the screening of vaccines and adjunct therapies aiming at the prevention and treatment of severe malaria. 相似文献
20.
Ernst K R?dland Morten Mattingsdal Ole K Olstad Reidun Ovsteb? Peter Kierulf Fredrik Muller Stig S Fr?land 《Medical mycology》2008,46(4):327-336
The objective of these studies was to investigate genes of importance in the pathogenesis of Aspergillus infections. To do so, we employed microarray methodology to explore gene expression in human monocytes infected with Aspergillus conidia as compared with unstimulated monocytes and those stimulated with lipopolysaccharide (LPS) signaling through TOLL-like receptor 4 (TLR4). We found 997 (P相似文献