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101.
102.
Hudelist G Köstler WJ Czerwenka K Kubista E Attems J Müller R Gschwantler-Kaulich D Manavi M Huber I Hoschützky H Zielinski CC Singer CF 《International journal of cancer. Journal international du cancer》2006,118(5):1126-1134
Her-2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti-Her-2/neu antibody trastuzumab (Herceptin(R)) has become a valuable therapeutic option for patients with Her-2/neu-overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her-2/neu and EGFR in 46 Her-2/neu-overexpressing tumor samples from trastuzumab-treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr-1248 Her-2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr-845 and (p)tyr-1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr-1248 Her-2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr-845, ptyr-1173 EGFR and EGFR did not. The presence of ptyr-1248 Her-2/neu and ptyr-845 or ptyr-1173 EGFR, however, was a strong predictor of both response to trastuzumab-based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr-845 EGFR and ptyr-1248 Her-2/neu were both independent predictors of progression-free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr-845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr-1248 Her-2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her-2/neu and EGFR are key determinants for trastuzumab efficacy. 相似文献
103.
Ko D Gu Y Yasunaga Y Nakamura K Srivastava S Moul JW Sesterhenn IA McLeod DG Arnstein P Taylor DO Hukku B Rhim JS 《International journal of oncology》2003,22(6):1311-1317
Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro models of prostate tumors representing primary tumors. The generation of immortalized primary prostate cancer cells that will accurately reflect the in situ characteristics of malignant epithelium is greatly needed. We have successfully established a neoplastic immortalized human prostate epithelial (HPE) cell culture derived from a primary tumor. The RC-9 cells transduced through infection with a retrovirus vector expressing the E6 and E7 genes (E6E7) of human papilloma virus-16 (HPV-16) are currently growing well at passage 40, whereas RC-9 cells senesced at passage 7. RC-9/E6E7 cells exhibit epithelial morphology and high level of telomerase activity. More importantly, these immortalized cells produced tumors (SCID5038D) when inoculated into SCID mice. RC-9/E6E7 cells and SCID-5038D cells exhibit a high level of telomerase activity and androgen-responsiveness when treated with R1881. Expression of prostate specific antigen (PSA), androgen receptor (AR), prostate stem cell antigen (PSCA), an androgen-regulated prostate specific gene (NKX3.1), p16, cytokeratins 8, 15 and HPV-16 E6 gene was detected in both of these cells. RC-9/E6E7 and SCID5038D cells also showed growth inhibition when exposed to retinoic acid and transforming growth factor (TGF)-beta1, potent inhibitors of prostate epithelial cell growth. A number of chromosome alterations were observed including the loss of chromosomes 2p, 3p, 8p, 13, 14, 16, 17, 18, 21 and the gain of 7 and 20 in the tumor cell line (SCID5038D). These results demonstrate that this primary tumor-derived HPE cell line retained its neoplastic phenotypes and its prostate-specific markers and should allow studies to elucidate molecular and genetic alterations involved in prostate cancer. This is the first documented case of a malignant AR and PSA positive established human prostate cancer cell line from a primary tumor of a prostate cancer patient. 相似文献
104.
Bleomycin hydrolase (Blh1p), a multi-sited thiol protease in search of a distinct physiological role
Bleomycin hydrolase, Blh1p, from yeast was co-purified with Gce1p, a cAMP-binding ectoprotein, anchored to the plasma membrane
by a glycosyl-phosphatidylinositol (GPI) anchor. Blh1p is a hydrophilic thiol protease lacking transmembrane domains. We have
used polyclonal antibodies to study the topology of the over-expressed protein in yeast and have found that it is amphitropic.
Part of Blh1p is associated with plasma membranes, and most of the rest occurs in the cytosol. Both the growth conditions
and calcium were found to have minor influences on the topology of Blh1p, in that glucose and the earth-alkali ion slightly
enhanced recruitment to the membrane. We have examined the possibility that co-purification of Blh1p with Gce1p has a functional
basis, and have observed that over-expression of BLH1 in yeast leads to an acceleration of the glucose-induced amphiphilic to hydrophilic conversion of Gce1p, wherein Blh1p could
either directly catalyse the proteolytic removal of the polar headgroup of the GPI anchor subsequent to an initial lipolytic
cleavage by a GPI-specific phospholipase C or indirectly modulate the reaction. The data show that a thiol protease is involved,
but point to an indirect role of Blh1p in GPI processing. Proteases with similar or overlapping substrate specificity are
likely to exist, since deletion of BLH1 neither entails a growth defect on any carbon source tested, nor the loss of proteolytic processing of the GPI anchor of
Gce1p. Reduced proteolytic GPI processing is, however, observed in the blh1 mutant and the corresponding acceleration in the respective BLH1 multi-copy transformant.
Received: 20 September 1996 / 23 April 1997 相似文献
105.
Pekrul Isabell Schachtner Thomas Zwißler Bernhard Möhnle Patrick 《Der Anaesthesist》2021,70(7):616-617
Die Anaesthesiologie - 相似文献
106.
Isabell Brikell Laura Ghirardi Brian M. D’Onofrio David W. Dunn Catarina Almqvist Søren Dalsgaard Ralf Kuja-Halkola Henrik Larsson 《Neuropsychopharmacology》2018,83(2):173-180
Background
Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.Methods
We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.Results
Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33–3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75–1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54–1.74), full siblings (OR = 1.56, 95% CI = 1.46–1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14–1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96–1.25), and cousins (OR = 1.15, 95% CI = 1.10–1.20). The genetic correlation was 0.21 (95% CI = 0.02–0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23–0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = ?0.16–0.79).Conclusions
This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders. 相似文献107.
108.
This report describes an underrecognized entity of the penis that is associated with chronic condom catheter use and phimosis. Our study group consisted of 7 patients who presented with polypoid or cauliflower-like masses that involved the glans penis or prepuce and that ranged in size from 2 to 7.5 cm in greatest dimension (median size, 2.5 cm). The majority of lesions affected the ventral surface of the glans, near the urethral meatus. The patients ranged in age from 25 to 58 years (median age, 40 years) at the time of initial surgical resection. The preoperative duration of the lesions ranged from 6 months to 10 years. Five patients had a history of long-term condom catheter use (duration: 5 to 21 years), and 1 patient had paraphimosis. The background history for 1 patient is unknown. Histologically, all specimens had a polypoid configuration and a keratinizing squamous epithelial surface. The underlying stroma was notably edematous, and there was vascular dilation of preexisting vessels, and in many instances, a focal mild small vessel proliferation. The stroma had mildly to moderately increased cellularity with mononucleated and multinucleated mesenchymal cells. A mild inflammatory infiltrate was often present. Two cases were examined with immunohistochemistry, and the stromal cells had limited immunoreactivity for muscle-specific actin, alpha-smooth muscle actin, and desmin and had no reactivity for S100 protein or CD34. Surgical intervention was local in all instances. Follow-up information was available for 5 of the 7 patients (71%), with a mean follow-up interval of 11 years 4 months. Two patients developed a local recurrence of the process at intervals of less than 1 years and 3 years 7 months. Both recurrent lesions were also managed by local excision. 相似文献
109.
Purdy IB 《Nursing forum》2004,39(4):25-33
TOPIC: In spite of the significance of vulnerable as a phenomenon that affects the human condition, its essence remains complex and elusive. PURPOSE: A conceptual analysis to clarify knowledge of this concept to explore the common and scientific usage. SOURCES OF INFORMATION: A comprehensive and systematic review from bibliographic and abstract databases and online searches. CONCLUSIONS: Findings contributed to the definition of vulnerable as a highly individualized dynamic process of being open to circumstances that positively or negatively influence outcomes, a definition based on a synthesis of knowledge concerning vulnerable, and offers a reconceptualization that expands its use in nursing scientific theory, research, and clinical practice. 相似文献
110.
Breidenbach M Rein DT Schöndorf T Khan KN Herrmann I Schmidt T Reynolds PN Vlodavsky I Haviv YS Curiel DT 《Cancer letters》2006,240(1):114-122
Gene therapy with adenoviral (Ad) vectors is a promising new approach in the treatment of cancer. Strategies to restrict adenoviral-mediated transgene expression are important to avoid gene transfer into normal cells. Heparanase (HPR) is overexpressed in breast cancer but downregulated in differentiated normal tissue. Expression of the HPR gene was evaluated in breast cancer cells. Biodistribution and liver tropism was evaluated in a mouse model. HPR is highly expressed in breast cancer tissue. The HPR promoter retained its fidelity in an adenovirus context and was activated in breast cancer cells but showed low activity in normal breast cells and the murine liver. We conclude that the HPR pathway is a promising target for the development of breast cancer directed gene therapy strategies. 相似文献