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51.
Kevin N Hascup Erin R Hascup Michelle L Stephens Paul EA Glaser Takashi Yoshitake Aleksander A Mathé Greg A Gerhardt Jan Kehr 《Neuropsychopharmacology》2011,36(8):1769-1777
Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (∼30%) and slow onset of action (2–4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2 Hz) and high spatial (15 × 333 μm) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression. Although no changes in glutamate dynamics were observed between 3 and 6 months FRL and FSL rats, a significant increase in resting glutamate levels was observed in the 12- to 15-month-old FSL rats compared with the 3- to 6-month-old FSL and age-matched FRL rats on days 3–5 post-implantation. Our MEA also recorded, for the first time, a unique phenomenon in all the four rat groups of fluctuations in resting glutamate, which we have termed glutamate transients. Although these events lasted only for seconds, they did occur throughout the testing paradigm. The average concentration of these glutamate-burst events was significantly increased in the 12- to 15-month-old FSL rats compared with 3- to 6-month-old FSL and age-matched FRL rats. These studies lay the foundation for future studies of both tonic and phasic glutamate signaling in rat models of depression to better understand the potential role of glutamate signaling in depression. 相似文献
52.
Clinical Impact of Tumour Involvement of the Anastomotic Doughnut in Oesophagogastric Cancer Surgery
K Sillah EA Griffiths SA Pritchard R Swindell CM West R Page IM Welch 《Annals of the Royal College of Surgeons of England》2009,91(3):195-200
INTRODUCTION
Published colorectal cancer surgery data suggest no role for the analysis of the anastomotic doughnuts following anterior resection. The usefulness of routine histological analysis of the upper gastrointestinal doughnut is not clear. Our study assessed the impact of cancer involvement of the doughnut on clinical practice. Factors associated with doughnut involvement and the effect on patients'' survival were also analysed.PATIENTS AND METHODS
The clinicopathological details of 462 patients who underwent potentially curative oesophagogastrectomy for cancer with a stapled anastomosis between 1994 and 2006 in two specialist centres were retrospectively analysed. Univariate, multivariate and survival analyses were carried out.RESULTS
Approximately 5% of doughnuts (22 of 462) were histologically involved with cancer. Microscopic involvement of the proximal resection margin, local lymph node metastasis and lymphatic invasion within the main resected specimen were independently associated with doughnut involvement (all P < 0.05). However, these three factors taken together failed to predict doughnut involvement. Doughnut involvement was an independent adverse prognostic factor for overall survival (P = 0.0013).CONCLUSIONS
In contrast to findings in colorectal surgery, doughnut involvement with cancer appears to have useful prognostic information following oesophagogastrectomy. Routine histological analysis of upper gastrointestinal doughnuts is justified. Doughnut involvement could potentially strengthen the indications for adjuvant therapy in the future. 相似文献53.
Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases 总被引:1,自引:1,他引:0 下载免费PDF全文
Huijts PE Vreeswijk MP Kroeze-Jansema KH Jacobi CE Seynaeve C Krol-Warmerdam EM Wijers-Koster PM Blom JC Pooley KA Klijn JG Tollenaar RA Devilee P van Asperen CJ 《Breast cancer research : BCR》2007,9(6):R78-9
Introduction
Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.Methods
We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.Results
Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.Conclusion
Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles. 相似文献54.
55.
Haixia Yu Bruce Bianchi Randy Metzger Kevin J. Lynch Elizabeth A. Kowaluk Michael F. Jarvis Tim van Biesen 《Drug development research》1999,48(2):84-93
Adenosine‐5′‐O‐3‐thio[35S]triphosphate ([35S]‐ATPγS) has been reported to specifically bind several P2X receptor subtypes, including P2X1, P2X2, P2X3, and P2X4. Similarly, adenosine‐5′‐O‐2‐thio[35S]diphosphate ([35S]‐ADPβS) has been reported to label putative P2Y receptors. To address whether these radioligands selectively label P2 receptors, the functional activity of various P2 ligands was compared with their ability to compete for [35S]‐ATPγS and [35S]‐ADPβS binding to cell membrane preparations from rat brain, HEK293 cells, and to native and P2X4 transfected 1321N1 astrocytoma cells. [35S]‐ATPγS (0.2 nM) and [35S]‐ADPβS (0.1 nM) displayed a high percentage of specific binding to membranes prepared from 1321N1 human astrocytoma cells, which were found to be devoid of detectable P2X and P2Y functional activity. [35S]‐ATPγS and [35S]‐ADPβS also exhibited equivalent high percentages of specific binding to HEK293 cell membranes, which endogenously express the P2Y1 and P2Y2 receptor subtypes, to 1321N1 cells stably transfected with the human P2X4 receptor, and to rat brain membranes, which have previously been shown to contain both P2X and P2Y receptor subtypes. The potency order of P2 agonists to compete for radioligand binding to these cell membrane preparations was significantly different from the functional rank order potencies determined in HEK293 cells and 1321N1 cells expressing the P2X4 receptor, as measured by cytosolic calcium flux. These data indicate that [35S]‐ATPγS and [35S]‐ADPβS appear to bind sites that do not correspond to known functional P2 receptor subtypes. The apparent lack of specificity of these radioligands for labeling P2 receptors is similar to that reported for other radiolabeled nucleotides and illustrates the need for caution in interpreting the apparent pharmacology of native P2 receptors on the basis of binding data alone. Drug Dev. Res. 48:84–93, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
56.
57.
The EuroQoL EQ-5D and MOS SF-36 are two generic quality of life measures that differ significantly in their design (the former being an index and the latter a profile). Both have been extensively used in evaluating interventions in acute disease. This study tested their comparative performance in a survey of patients with relapsing-remitting multiple sclerosis (MS).
METHODS: 309 patients with diagnosed relapsing-remitting MS were identified through the records of 5 specialist centers in North West England. Patients were contacted by telephone by a specialist MS nurse and asked to complete a set of questionnaires distributed by mail. The questionnaire booklet reproduced the English version of SF-36, together with the EQ-5D and a self completion form of the Barthel. Minimal additional background information was obtained from all respondents; 4 weeks following their completion of the initial booklet, a second identical booklet was sent to the first 200 initial respondents. Patients in this re-test sub-group were asked whether their health status had improved, deteriorated, or remained unchanged over the intervening period.
RESULTS: Of the 200 patients in the test/re-test subgroup, 144 (72%) replied on both occasions. Paired t-tests for the PCS, MCS, and general health perception scores on the SF-36 failed to generate comprehensive evidence of reliability. The weighted index form of the EQ-5D and the visual analogue scale self-ratings provided superior evidence of reliability. Standardized response means for both measures confirmed this general pattern.
CONCLUSION: EQ-5D performs satisfactorily as a generic measure of health-related quality of life in patients with MS. 相似文献
METHODS: 309 patients with diagnosed relapsing-remitting MS were identified through the records of 5 specialist centers in North West England. Patients were contacted by telephone by a specialist MS nurse and asked to complete a set of questionnaires distributed by mail. The questionnaire booklet reproduced the English version of SF-36, together with the EQ-5D and a self completion form of the Barthel. Minimal additional background information was obtained from all respondents; 4 weeks following their completion of the initial booklet, a second identical booklet was sent to the first 200 initial respondents. Patients in this re-test sub-group were asked whether their health status had improved, deteriorated, or remained unchanged over the intervening period.
RESULTS: Of the 200 patients in the test/re-test subgroup, 144 (72%) replied on both occasions. Paired t-tests for the PCS, MCS, and general health perception scores on the SF-36 failed to generate comprehensive evidence of reliability. The weighted index form of the EQ-5D and the visual analogue scale self-ratings provided superior evidence of reliability. Standardized response means for both measures confirmed this general pattern.
CONCLUSION: EQ-5D performs satisfactorily as a generic measure of health-related quality of life in patients with MS. 相似文献
58.
H. J. Stein M.D. W. K. H. Kauer M.D. H. Feussner M.D. J. R. Siewert M.D. EA.C.S. 《Journal of gastrointestinal surgery》1998,2(4):333-341
Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett’s esophagus, but clinical studies
in patients with adenocareinoma arising in Barrett’s esophagus are lacking. Ambulatory esophageal measurement of acid and
bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH
probe in 20 asymptomatie volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients
with GERD and erosive esophagitis, 33 patients with GERD and Barrett’s esophagus, and 14 patients with early adenocarcinoma
arising in Barrett’s esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after
laparoscopie Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients
without esophagitis to those with erosive esophagitis and benign Barrett’s esophagus and was highest in patients with early
carcinoma in Barrett’s esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients
with benign Barrett’s esophagus and 11 (78.6%) of 14 patients with early adenoearcinoma in Barrett’s esophagus. Nissen fundoplieation
but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly
prevalent in patients with Barrett’s esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed
by Nissen fundoplication but not medical acid suppression alone. (J GASTROINTEST SURG 1998;2:333-341.)
Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14,
1997 相似文献
59.
Leeksma OC; Meijer-Huizinga F; Stoepman-van Dalen EA; van Ginkel CJ; van Aken WG; van Mourik JA 《Blood》1986,67(5):1460-1467
Concentrations of plasma fibrinopeptide A (FPA) were measured by radioimmunoassay in 50 patients with venous thromboembolism or disseminated intravascular coagulation or both. A consistent discrepancy was observed in values obtained with two anti-FPA antisera. Analysis of extracts from plasma of these patients by high-performance liquid chromatography (HPLC) revealed the presence of a phosphorylated and an unphosphorylated form of the A peptide. Differences in concentrations of FPA measured with the two antisera could be accounted for by their different reactivity with phosphorylated FPA (FPA-P). The differences were abolished by treatment with alkaline phosphatase. A good correlation was observed between the FPA-P content of free A- peptide material and of fibrinogen in plasma as determined by HPLC (r = .88, P less than .001, n = 11). In patients with elevated FPA levels, the mean FPA-P content of fibrinogen was significantly higher (P less than .002, n = 13) than in patients with normal FPA levels (n = 8) and in healthy controls (n = 14). Phosphorus in fibrinogen did not correlate with fibrinogen degradation products or fibrinogen levels and became normal on adequate anticoagulation. Therefore, blood-clotting activation may lead to a high phosphate content of fibrinogen and of free FPA in plasma. 相似文献
60.
We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA- binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA- binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma. 相似文献