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21.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
22.
Human mini-chromosomes in mouse embryonal stem cells 总被引:3,自引:2,他引:3
We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb
in size into mouse embryonal stem cells. Although these human mini-
chromosomes are stable in hamster and chicken cells, they re-arrange or
segregate aberrantly in the embryonal stem cells and are rapidly lost in
the absence of selection. However, one of the mini-chromosomes re-
arranged, acquired mouse centromeric sequences and was then stably
maintained for at least 60 population doublings in culture. This mini-
chromosome, which is 4 Mb in size, is a candidate for a mouse germ line
chromosome vector.
相似文献
23.
Louise R Rodino-Klapac Paul ML Janssen Chrystal L Montgomery Brian D Coley Louis G Chicoine K Reed Clark Jerry R Mendell 《Journal of translational medicine》2007,5(1):45-11
Background
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. 相似文献24.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
25.
A Aronstam P J Kirk J McHardy J W Culver-James D S McLellan P Turk S G Rainsford M Slattery 《Journal of clinical pathology》1977,30(1):65-67
Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use. 相似文献
26.
Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings. 相似文献
27.
A simple method to improve the accuracy of non-invasive ultrasound in selecting TIA patients for cerebral angiography. 总被引:2,自引:2,他引:0
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P Humphrey P Sandercock J Slattery 《Journal of neurology, neurosurgery, and psychiatry》1990,53(11):966-971
A prospective study is reported of the ability of B mode ultrasound imaging and continuous wave Doppler flow studies to detect different degrees of stenosis of the extracranial internal carotid artery (ICA) in 186 arteries in 99 patients with transient ischaemic attacks (TIA) and minor ischaemic stroke. A simple mathematical equation has been developed which combines the image and flow data to provide a single predictor of the degree of angiographic stenosis which has advantages over either ultrasonic modality used alone. The sensitivity and specificity of the predictive model in the detection of stenosis greater than or equal to 25% was 73% and 98%, of stenosis greater than or equal to 50% was 90% and 93%, of stenosis greater than or equal to 75%, 65% and 99% and occlusion 100% and 94% respectively. The principal clinical value of ultrasound screening is to spare patients with "non-significant" stenosis the risk of unnecessary angiography. Thus a simple measure of the Duplex screening tests' performance is the proportion of all strokes occurring as a complication of angiography that are avoided by changing the investigation policy from "angiograms for all carotid TIA and minor ischaemic stroke patients" to "angiograms for all patients with abnormal ultrasound results". If Duplex scanning were used to select patients most likely to have a significant abnormality on angiography, depending on the degree of stenosis to be detected, 52-85% of angiographic strokes might be avoided. If the predictive equation were used 62-88% of angiographic strokes might be avoided. 相似文献
28.
Needle biopsy of renal allografts: comparison of two techniques 总被引:2,自引:0,他引:2
Bogan ML; Kopecky KK; Kraft JL; Holladay AO; Filo RS; Leapman SB; Thomalla JV 《Radiology》1990,174(1):273-275
Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications. 相似文献
29.
Plant foods and colon cancer: an assessment of specific foods and their related nutrients (United States) 总被引:3,自引:0,他引:3
Martha L. Slattery John D. Potter Ashley Coates Khe-Ni Ma T. Dennis Berry Debra M. Duncan Bette J. Caan 《Cancer causes & control : CCC》1997,8(5):575-590
Plant foods have been associated inversely with colon cancer. Since amajor focus of this study was to identify components of plant foods whichmay account for their association with colon cancer, nutrients which arecommonly found in plant foods also were evaluated. A population-basedcase-control study was conducted in Northern California, Utah, and the TwinCities area of Minnesota (United States). Complete data were available frominterviewer-administered questionnaires on 1,993 cases and 2,410 controls.Higher intakes of vegetables (for highest relative to lowest quintile ofintake) were associated inversely with colon cancer risk: the odds ratio(OR) was 0.7 for both men (95 percent [CI] confidence interval = 0.5-0.9)and women (CI = 0.5-1.0). Associations were stronger among those withproximal tumors. Total fruit intake was not associated with colon cancerrisk although, among men, higher levels of whole grain intake wereassociated with a decreased risk (OR = 0.6, CI = 0.4-0.9 for older men);high intakes of refined grains were associated with an increased risk (OR =1.5, CI = 1.1-2.1). Dietary fiber intake was associated with a decreasedrisk of colon cancer: OR = 0.5 (CI = 0.3-0.9) for older men; OR = 0.7 (CI =0.4-1.2) for older women; OR = 0.6 (CI = 0.4-1.0) for men with proximaltumors; OR = 0.5 (CI = 0.3-0.9) for women with proximal tumors. Othernutrients, for which plant foods were the major contributor - such asvitamin B6, thiamin, and niacin (women only) - also were associatedinversely with colon cancer. Neither beta-carotene nor vitamin C wasprotective for colon cancer. Adjustment of plant foods for nutrients foundin plant foods or for supplement use did not appreciably alter the observedassociations between plant foods and colon cancer. 相似文献
30.