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41.
Lee E. Moore Marcella L. Warner Allan H. Smith David Kalman Martyn T. Smith 《Environmental and molecular mutagenesis》1996,27(3):176-184
The exfoliated cell micronucleus (MN) assay using fluorescent in situ hybridization (FISH) with a centromeric probe is a rapid method for determining the mechanism of MN formation in epithelial tissues exposed to carcinogenic agents. Here, we describe the use of this assay to detect the presence or absence of centromeric DNA in MN induced in vivo by radiation therapy and chronic arsenic (As) ingestion. We examined the buccal cells of an individual receiving 6,500 rads of photon radiation to the head and neck. Exfoliated cells were collected before, during, and after treatment. After radiation exposure a 16.6-fold increase in buccal cell MN frequency was seen. All induced MN were centromere negative (MN −) resulting from chromosome breakage. This finding is consistent with the clastogenic action of radiation and confirmed the reliability of the method. Three weeks post-therapy, MN frequencies returned to baseline. We also applied the assay to exfoliated bladder cells of 18 people chronically exposed to high levels of inorganic arsenic (In-As) in drinking water (average level, 1,312 μg As/L) and 18 matched controls (average level, 16 μg As/L). The combined increase in MN frequency was 1.8-fold (P = 0.001, Fisher's exact test). Frequencies of micronuclei containing acentric fragments (MN −) and those containing whole chromosomes (MN+) both increased (1.65-fold, P = 0.07, and 1.37-fold, P = 0.15, respectively), suggesting that arsenic may have both clastogenic and weak aneuploidogenic properties in vivo. After stratification on sex, the effect was stronger in male than in female bladder cells. In males the MN-frequency increased 2.06-fold (P = 0.07) while the frequency of MN+ increased 1.86-fold (P = 0.08). In addition, the frequencies of MN − and MN+ were positively associated with urinary arsenic and its metabolites. However, the association was stronger for micronuclei containing acentric fragments. By using FISH with centromeric probes, the mechanism of chemically induced genotoxicity can now be determined in epithelial tissues. © 1996 Wiley-Liss, Inc. 相似文献
42.
Physical and psychological trauma which results in mood disorders and the disruption of complex behaviours is associated with reductions in hippocampal volume. Clinical evaluation of neuropathic pain reveals mood and behavioural change in a significant number of patients. A rat model of neuropathic injury results in complex behavioural changes in a subpopulation (~30%) of injured rats; these changes are co‐morbid with a range of other ‘disabilities’. The specific objective of this study was to determine in rats the morphology of the hippocampus and dentate gyrus in individuals with and without complex behavioural disruptions following a constriction injury of the sciatic nerve, and to determine whether rats that develop disabilities following nerve injury have a reduced hippocampal volume compared with injured rats with no disabilities. The social behaviours of nerve‐injured rats were evaluated before and after nerve injury. The morphology of the hippocampus of rats with and without behavioural disruptions was compared in serial histological sections. Single‐housing and repeated social‐interaction testing had no effect on the morphology of either the hippocampus or the dentate gyrus. Rats with transient or ongoing disability identified by behavioural disruption following sciatic nerve injury, show bilateral reductions in hippocampal volume, and lateralised reduction in the dentate gyrus (left side). Disabled rats display a combination of behavioural and physiological changes, which resemble many of the criteria used clinically to diagnose mood disorders. They also show reductions in the volume of the hippocampus similar to people with clinically diagnosed mood disorders. The sciatic nerve injury model reveals a similarity to the human neuropathic pain presentation presenting an anatomically specific focus for the investigation of the neural mechanisms underpinning the co‐morbidity of chronic pain and mood disorder. 相似文献
43.
Bekesi G Tulassay Z Lengyel G Schaff Z Szombath D Stark J Marczell I Nagy-Repas P Adler I Dinya E Racz K Magyar K 《Journal of neural transmission (Vienna, Austria : 1996)》2012,119(1):25-30
Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague?CDawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet?+?selegiline and (4) normal rat food?+?selegiline. Selegiline solution (2.5???g/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20?C30?ml/day), the daily dose was roughly equal with that used in the human therapy (5?C10?mg/day). TSC was determined both at the beginning (0?day) and at the end of the study (28?days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers. 相似文献
44.
45.
Changhyun Kim B.S. Brittany G. Craiglow M.D. Kalman L. Watsky M.D. Richard J. Antaya M.D. 《Pediatric dermatology》2015,32(4):e161-e162
A 17‐year‐old boy presented with recurring severe dermatitis of the face of 5‐months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris. 相似文献
46.
The effects of somatostatin or the somatostatin analog SMS 201–995 were studied on 4 densely granulated somatotroph adenomas
and 4 sparsely granulated somatotroph adenomas in vitro. Release of growth hormone (GH) into culture media during incubation
with somatostatin or SMS 201 -995 were measured by radioimmunoassay, and light-microscopical and ultrastructural morphometric
parameters were compared with those of cultured control somatotroph adenoma cells of the same tumor. In all tumors except
for 1 densely granulated somatotroph adenoma, somatostatin or SMS 201–995 decreased GH release into culture media in 24- and
2-hour incubations. After 48-hour incubation with somatostatin or SMS 201–995, there was no change in cell size or secretory
granule diameter. One densely granulated adenoma showed decreased cytoplasmic volume density (CVD) of Golgi apparatus and
secretory granules, and a sparsely granulated adenoma had reduced CVD of endoplasmic reticulum. All the tumors that responded
with decreased GH release exhibited increased CVD of lysosomes after incubation with somatostatin or SMS 201–995. These results
indicate that both densely and sparsely granulated somatotroph adenomas respond to somatostatin inhibition and, furthermore,
that inhibition of hormone release is associated with accumulation of lysosomes, suggesting lysosomal degradation of stored
hormone.
Hospital 20 Nov. (ISSSTE) Coyoacan y Felix Cuevas, Colonia del Valle and (Dept Patologia) y Hospital de Especialidades (C.M.N.,
IMSS) Cuauhtemoc y Dr. Marquez, Mexico City (IF). 相似文献
47.
Rapid decline in acute stimulation thresholds with steroid-eluting active-fixation pacing leads 总被引:1,自引:0,他引:1
Kistler PM Kalman JM Fynn SP Singarayar S Roberts-Thomson KC Lindsay CB Khong U Sparks PB Strathmore N Mond HG 《Pacing and clinical electrophysiology : PACE》2005,28(9):903-909
BACKGROUND AND AIM: There is an increasing use of active-fixation leads for cardiac pacing, yet concerns remain regarding initial high stimulation thresholds. The aim was to perform a detailed analysis of pacing parameters at the time of implantation to determine when lead repositioning should be considered. METHODS: We performed a prospective observational study of consecutive new pacemaker implants. Detailed analysis of pacing parameters was collected at 2-minute intervals for 10 minutes, and at day 1 and week 8 following implant. RESULTS: Ninety-four patients underwent implantation of 79 dual-chamber and 15 single-chamber pacemakers using active-fixation leads in both chambers. An initial threshold of >1 V was demonstrated in 45/94 (48%) ventricular leads (mean threshold 1.5 +/- 0.3 V). This declined rapidly to 0.9 +/- 0.3 V at 4 minutes (P < 0.01), 0.7 +/- 0.3 V at 10 minutes (P < 0.01), and 0.6 +/- 0.3 V at day 1 (P < 0.01). At day 1, 43/45 leads were <1 V. There were 79 atrial leads. An initial threshold of >1 V (mean 1.7 +/- 0.6 V) was demonstrated in 41/79 (52%) leads falling significantly to 1.1 +/- 0.5 V at 4 minutes (P < 0.01), 0.9 +/- 0.4 V at 10 minutes (P < 0.01), and 0.6 +/- 0.2 V at day 1 (P < 0.01). At 10 minutes, 32 of 41 leads demonstrated a threshold of <1 V with all leads <1 V at day 1. Thresholds were maintained medium term. CONCLUSIONS: Active-fixation leads are commonly associated with initially high thresholds that fall rapidly. An initial threshold of 2 V should be provisionally accepted and retested at 4 minutes. The majority will have a threshold of <1 V the following day. A failure of a high threshold to decline at 4 minutes requires lead repositioning. 相似文献
48.
Pratt VM Zehnbauer B Wilson JA Baak R Babic N Bettinotti M Buller A Butz K Campbell M Civalier C El-Badry A Farkas DH Lyon E Mandal S McKinney J Muralidharan K Noll L Sander T Shabbeer J Smith C Telatar M Toji L Vairavan A Vance C Weck KE Wu AH Yeo KT Zeller M Kalman L 《The Journal of molecular diagnostics : JMD》2010,12(6):835-846
Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci (CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6. The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci (CYP4F2, EPHX1, ABCB1, HLAB, KIF6, CYP3A4, CYP3A5, TPMT, and DPD) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research. 相似文献
49.
Microvascular structural entropy: A novel approach to assess angiogenesis in pituitary tumors 总被引:2,自引:0,他引:2
Entropy, a measure of the degree of disorder in a system, has recently been used in different morphologic studies to quantify
regularity. Our aims were (a) to study the structural organization of the microvascular bed in prolactin (PRL)-producing adenomas
and carcinomas, the most vascularized of pituitary tumors, by assessing microvascular structural entropy (MSE), and (b) to
determine whether the degree of disorder of the capillary bed correlates with tumor cell proliferation as estimated by MIB-1
labeling, microvessel density (MVD), the most widely used method of quantifying blood vessel formation, and various clinicopathologic
parameters (gender, age, tumor size and invasiveness). The morphometric study demonstrated statistically significant differences
in MIB-1 labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB-1 labeling index (PRL-producing
adenomas 1.5±0.27; carcinomas 15.0±4.04) and MVD (PRL-producing adenomas 2.7±0.34; carcinomas 4.2±0.72), the MSE values were
significantly higher in adenomas (171.5±25.37) than in carcinomas (67.9±17.45). These results indicate that PRL-producing
carcinomas have a less chaotic distribution of vessels than benign adenomas. In contrast to a lack of correlation between,
microvessel density and other morphometric parameters, a strong negative correlation was found between MSE and MIB-1 labeling
index (r=0.511, p=0.003). It thus appears that regular, less chaotic microvascular geometry contributes to increased proliferative activity
in PRL cell tumors. Analysis of MSE may provide an independent parameter of tumor behavior, and contributes to a better understanding
of the role of microvasculature in pituitary tumor progression. 相似文献
50.
Klapproth JM Sasaki M Sherman M Babbin B Donnenberg MS Fernandes PJ Scaletsky IC Kalman D Nusrat A Williams IR 《Infection and immunity》2005,73(3):1441-1451
Previously, we have identified a large gene (lifA, for lymphocyte inhibitory factor A) in enteropathogenic Escherichia coli (EPEC) encoding a protein termed lymphostatin that suppresses cytokine expression in vitro. This protein also functions as an adhesion factor for enterohemorrhagic E. coli (EHEC) and Shiga toxin-producing E. coli and is alternatively known as efa1 (EHEC factor for adherence 1). The lifA/efa1 gene is also present in Citrobacter rodentium, an enteric pathogen that causes a disease termed transmissible murine colonic hyperplasia (TMCH), which induces colitis and massive crypt cell proliferation, in mice. To determine if lifA/efa1 is required for C. rodentium-induced colonic pathology in vivo, three in-frame mutations were generated, disrupting the glycosyltransferase (GlM12) and protease (PrMC31) motifs and a domain in between that does not encode any known activity (EID3). In contrast to infection with wild-type C. rodentium, that with any of the lifA/efa1 mutant strains did not induce weight loss or TMCH. Enteric infection with motif mutants GlM12 and PrM31 resulted in significantly reduced colonization counts during the entire 20-day course of infection. In contrast, EID3 was indistinguishable from the wild type during the initial colonic colonization, but cleared rapidly after day 8 of the infection. The colonic epithelium of all infected mice displayed increased epithelial regeneration. However, significantly increased regeneration was observed by day 20 only in mice infected with the wild-type in comparison to those infected with lifA/efa1 mutant EID3. In summary, lifA/efa1 is a critical gene outside the locus for enterocyte effacement that regulates bacterial colonization, crypt cell proliferation, and epithelial cell regeneration. 相似文献