全文获取类型
收费全文 | 6210篇 |
免费 | 398篇 |
国内免费 | 67篇 |
专业分类
耳鼻咽喉 | 60篇 |
儿科学 | 131篇 |
妇产科学 | 59篇 |
基础医学 | 1045篇 |
口腔科学 | 74篇 |
临床医学 | 519篇 |
内科学 | 1143篇 |
皮肤病学 | 124篇 |
神经病学 | 729篇 |
特种医学 | 353篇 |
外科学 | 929篇 |
综合类 | 56篇 |
一般理论 | 3篇 |
预防医学 | 156篇 |
眼科学 | 241篇 |
药学 | 400篇 |
中国医学 | 14篇 |
肿瘤学 | 639篇 |
出版年
2024年 | 4篇 |
2023年 | 50篇 |
2022年 | 96篇 |
2021年 | 144篇 |
2020年 | 113篇 |
2019年 | 138篇 |
2018年 | 148篇 |
2017年 | 118篇 |
2016年 | 181篇 |
2015年 | 225篇 |
2014年 | 252篇 |
2013年 | 324篇 |
2012年 | 469篇 |
2011年 | 476篇 |
2010年 | 303篇 |
2009年 | 281篇 |
2008年 | 417篇 |
2007年 | 449篇 |
2006年 | 407篇 |
2005年 | 425篇 |
2004年 | 385篇 |
2003年 | 339篇 |
2002年 | 286篇 |
2001年 | 72篇 |
2000年 | 46篇 |
1999年 | 36篇 |
1998年 | 70篇 |
1997年 | 44篇 |
1996年 | 50篇 |
1995年 | 30篇 |
1994年 | 44篇 |
1993年 | 31篇 |
1992年 | 14篇 |
1991年 | 19篇 |
1990年 | 9篇 |
1989年 | 19篇 |
1988年 | 17篇 |
1987年 | 9篇 |
1986年 | 13篇 |
1985年 | 12篇 |
1984年 | 11篇 |
1983年 | 16篇 |
1982年 | 17篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1978年 | 8篇 |
1977年 | 6篇 |
1972年 | 6篇 |
1965年 | 4篇 |
排序方式: 共有6675条查询结果,搜索用时 15 毫秒
71.
Multivariate Analysis of Risk Factors for Postoperative Complications in Benign Goiter Surgery: Prospective Multicenter Study in Germany 总被引:12,自引:5,他引:7
Thomusch O Machens A Sekulla C Ukkat J Lippert H Gastinger I Dralle H 《World journal of surgery》2000,24(11):1335-1341
Risk factors for postoperative complications of benign goiter surgery have not been investigated systematically. To this
end, a prospective multicenter study (January 1 through December 31, 1998) was conducted involving 7266 patients with surgery
for benign goiter from 45 East German hospitals. High-volume providers (>150 operations per year) performed 69% (5042/7266),
intermediate-volume providers 27% (50–150), and low-volume providers 4% (258/7266) of operations. Among the hospital groups,
the pattern of thyroid disease did not vary significantly, but there was a trend that small-volume providers tended to perform
more operations for uninodular goiter and high-volume providers treated more patients with Graves' disease and recurrent goiter.
Extent of resection (p < 0.0001) and remnant size (multinodular goiter and recurrent goiter, p < 0.001), differed significantly, with total thyroidectomy being performed more often in hospitals with more than 150 operations
compared to hospitals with an operative volume of less than 150 procedures per year. Despite the larger extent of resection
and smaller remnant size, rates of recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism were not increased. When the
logistic regression analyses were fitted to evaluate the impact of risk factors on transient and permanent RLN palsy and hypoparathyroidism,
larger extent of resection [relative risk (RR) 1.5–2.1] and recurrent goiter (RR 1.8–3.4) consistently evolved as independent
risk factors. With hypoparathyroidism, additional significant factors included patient gender (RR 2.1–2.4), hospital operative
volume (RR 0.8–1.5), and Graves' disease (RR 2.8). Unlike parathyroid gland identification during hypoparathyroidism, RLN
identification (RR 1.6) significantly (p= 0.01) reduced permanent RLN palsy rates. The multivariate analyses clearly confirmed the pivotal role of routine RLN identification,
independent of the extent of the thyroid resection. These findings might help hospitals with lower operative volumes to identify
patients at increased risk whom they might consider for specialist care. 相似文献
72.
Carsten Denkert Wilko Weichert Klaus-Jürgen Winzer Berit-Maria Müller Aurelia Noske Silvia Niesporek Glen Kristiansen Hans Guski Manfred Dietel Steffen Hauptmann 《Clinical cancer research》2004,10(16):5580-5586
PURPOSE: The human ELAV (embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellular mRNAs that contain AU-rich elements in their 3'-untranslated region. Cell culture studies have shown that the mRNA of cyclooxygenase (COX)-2 can be stabilized by HuR. EXPERIMENTAL DESIGN: To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to overexpression of COX-2, we studied expression of HuR in 208 primary breast carcinomas by immunohistochemistry. RESULTS: There were two different staining patterns of HuR in tumor tissue of breast carcinomas: nuclear expression was seen in 61% of cases; and an additional cytoplasmic expression was seen in 30% of cases. Expression of HuR was significantly associated with increased COX-2 expression; this association was particularly significant for cytoplasmic HuR expression (P < 0.0005). We further observed a significant association of cytoplasmic (P = 0.002) or nuclear HuR (P = 0.027) expression with increased tumor grade. Only 13% of the grade 1 carcinomas showed cytoplasmic expression of HuR, compared with 46% of the grade 3 carcinomas. There was no significant correlation between HuR expression and other clinicopathological parameters such as histological type, tumor size, or nodal status as well as patient survival. CONCLUSIONS: Our results suggest that overexpression of HuR in tumor tissue may be part of a regulatory pathway that controls the mRNA stability of several important targets in tumor biology, such as COX-2. Based on our results, additional studies are necessary to investigate whether HuR might be a potential target for molecular tumor therapy. 相似文献
73.
Regine Schneider-Stock Carsten Boltze Jerzy Lasota Markku Miettinen Brigitte Peters Matthias Pross Albert Roessner Thomas Günther 《Journal of clinical oncology》2003,21(9):1688-1697
PURPOSE: Gastrointestinal stromal tumors (GISTs) represent a distinctive (but histologically heterogeneous) group of neoplasms, the malignant potential of which is often uncertain. To determine the prognostic relevance of p16INK4 alterations in GISTs, we investigated a larger group of GISTs and correlated the genetic findings with clinicopathological factors and patient survival. MATERIAL AND METHODS: We evaluated the methylation status of the promotor by methylation-specific polymerase chain reaction (PCR), the presence of mutations by PCR-SSCP-sequencing, the loss of heterozygosity at the p16INK4 locus (using the c5.1 marker), and the immunohistochemical expression of p16INK4 protein in 43 GISTs in 39 patients. RESULTS: p16INK4 alterations were found in 25 of 43 GISTs (58.1%), with benign, borderline, or malignant GISTs showing no differences in the type and frequency of alteration. p16INK4 alterations were correlated with a loss of p16INK4 protein expression (P <.01). Patients who had tumors with p16INK4 alterations had a poorer prognosis than patients with tumors without such alterations (P =.02). There was a high predictive value for p16INK4 alterations only in the group of benign and borderline GISTs (P <.01) with regard to clinical outcome. Univariate Cox's proportional hazard regression analysis revealed a strong correlation between p16INK4 alterations, tumor size, mitotic index, and overall survival (P <.02), whereas multivariate Cox's analysis confirmed only p16INK4 alterations as an independent prognostic factor. CONCLUSION: We believe that the evaluation of p16INK4 alteration status is a helpful prognosticator, particularly in the benign and borderline groups of GISTs. 相似文献
74.
Frank Mayer Hans Stoop George L Scheffer Rik Scheper J Wolter Oosterhuis Leendert H J Looijenga Carsten Bokemeyer 《Clinical cancer research》2003,9(2):767-773
PURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways may influence the efficacy of chemotherapy. Their impact has not been investigated in a comprehensive study of tumor samples from clinically defined subgroups of GCT patients. EXPERIMENTAL DESIGN: We investigated proteins involved in regulation of apoptosis (p53, BAX, BCL-2, and BCL-X(L)), cell cycle control [p21 and retinoblastoma protein (RB)], and drug export and inactivation [P-glycoprotein, multidrug resistance-associated protein (MRP) 1, MRP2, breast cancer resistance protein, lung resistance protein, metallothionein, and glutathione S-transferase pi] immunohistochemically in samples of unselected GCT patients (n = 20), patients with advanced metastatic disease in continuous remission after first-line chemotherapy (n = 12), and chemotherapy-refractory patients (n = 24). Mature teratoma components (n = 10) within tumor samples from all groups were analyzed separately. The apoptotic index was studied by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: Invasive GCTs of all groups showed a correlation between wild-type p53 and apoptotic index (r(s) = 0.66; P < 0.001). The levels of the antiapoptotic proteins BCL-2 and BCL-X(L) were generally low. p21 was hardly detectable and did not correlate with p53 (r(s) = 0.29; P = 0.07). No significant differences among the three patient groups were identified regarding any of the investigated parameters (all Ps were >0.08), even though only individual samples from chemotherapy-resistant cases showed a strong staining for MRP2 and GSTpi. In contrast to other components, mature teratomas showed an intense p21 and RB staining and were mostly positive for MRP2, lung resistance protein, and GSTpi. CONCLUSIONS: Our results indicate a multifactorial basis for the chemosensitivity of GCTs with lack of transporters for cisplatin, of antiapoptotic BCL-2 family members, of p21 induction by p53, and of RB and an intact apoptotic cascade downstream of p53. These findings suggest a preference for apoptosis over cell cycle arrest after up-regulation of p53. None of the examined parameters offers a general explanation for the chemotherapy-resistant phenotype of refractory tumors. The up-regulation of various factors interfering with chemotherapy efficacy and ability for a p21-induced cell cycle arrest may explain the intrinsic chemotherapy resistance of mature teratomas. 相似文献
75.
Arif JM; Gairola CG; Glauert HP; Kelloff GJ; Lubet RA; Gupta RC 《Carcinogenesis》1998,19(8):1515-1517
The present study investigated the effects of dietary oltipraz on cigarette
smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats
were exposed daily to sidestream cigarette smoke in a whole- body exposure
chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained
on control diet while another group received the same diet supplemented
with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz,
starting 1 week prior to initiation of smoke exposure until the end of the
experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated
32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5
predominated in both the lung and the heart while adduct nos 3 and 2
predominated in the trachea and bladder, respectively. Quantitative
analysis revealed that the total adduct level was the highest in lungs
(270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48
adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides)
and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz
treatment reduced the adduct levels in lungs and bladder by >60%, while
the reduction in lungs in the low-dose group was approximately 35%. In
trachea, the effect of low and high dietary oltipraz on smoke DNA adduction
was equivocal, while smoke-related DNA adducts in the heart were minimally
inhibited by high-dose oltipraz. In a repeat experiment that employed a
3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to
inhibit the formation of DNA adducts in rat lungs and trachea by 80 and
65%, respectively. These data clearly demonstrate a high efficacy of
oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts
in the target tissues.
相似文献
76.
Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog 总被引:8,自引:0,他引:8
Inactivation of the p53 tumor suppressor gene has been implicated in the
pathogenesis of numerous human cancers, including osteosarcomas.
Appendicular osteosarcomas of the dog appear to be a good model for their
human equivalent with regard to biologic behavior, epidemiology and
histopathology. We individually screened exons 5-8 of the p53 gene for
mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to
compare the role of this gene in human and canine osteosarcoma
tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with
one tumor possessing two mutations within different exons. Of these, seven
were missense mutations and the eighth was a 'silent' mutation potentially
affecting the exon 6-7 splicing region. Five of the missense mutations were
located in highly conserved regions IV and V, while another corresponded
with the highly conserved codon 220 mutational hotspot located outside the
conserved domains. The locations and types of mutations were nearly
identical to those reported in human cancer. These findings provide strong
evidence of the involvement of p53 mutations in the development of canine
appendicular osteosarcomas. Canine osteosarcomas appear to be a promising
model for their human equivalent on a clinical, pathologic, and molecular
level.
相似文献
77.
Lise Borgwardt Liselotte H?jgaard Henrik Carstensen Henning Laursen Markus Nowak Carsten Thomsen Kjeld Schmiegelow 《Journal of clinical oncology》2005,23(13):3030-3037
PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use. 相似文献
78.
79.