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991.
Many others cancer agents can lead to cardiovascular toxicity apart from anthracyclines, 5-fluorouracil, trastuzumab and ionizing radiations. Paclitaxel, high-dose cyclophosphamide and ifosfamide, mitomycin and irinotecan cardiotoxicity is unusual but for certain. Hormonal therapy is extensively used in breast and prostate cancers. Thromboembolic and cardiovascular events are increased by estrogens, synthetic progestatives and tamoxifene. Because of major toxicities related to intravenous interleukin-2, subcutaneous interleukin-2 regimens have been developed, allowing an improvement of cardiovascular tolerability. Interferon is less frequently associated with cardiotoxicity. Before treatment initiation, risk factors favouring cardiac toxicity should be evaluated. These risk factors can be related to the cancer agent, to the patient or to the tumour. Uncommon toxic events in general population can be more frequent in high risk patients. Therapeutic option can be influenced by these uncommon toxic events in high risk patients. 相似文献
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Contributions of NMDA receptors to network recruitment and rhythm generation in spinal cord cultures 总被引:1,自引:0,他引:1
N-methyl-d-aspartic acid (NMDA) receptors are implicated in fictive locomotion; however, their precise role there is not clear. In cultures of dissociated cells from foetal rat spinal cord, synchronous bursting (but not fictive locomotion) can be induced by disinhibition, which is produced by blocking glycinergic and gamma-aminobutyric acid (GABA)A-dependent synaptic conductances. In this study, we investigate the role of NMDA-R in rhythm generation during disinhibition with multielectrode arrays and patch-clamp. We previously determined that bursting activity is generated by repetitive recruitment of a network through recurrent excitation. Blocking NMDA-R with d(-)-2-amino-5-phosphonopentanoic acid (APV) decreased the burst duration, suggesting a role of such receptors in the maintenance of high network activity during the bursts. In addition, APV reduced burst rate in about a third of the experiments, suggesting a contribution of NMDA-R in network recruitment. When (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA)/kainate receptors were blocked with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the presence of disinhibition, the burst rate was reduced and burst onset was slowed in two-thirds of the experiments. In the remaining experiments, bursting ceased completely with CNQX. Neither APV nor CNQX changed the spatial patterns of activity in the network, suggesting a co-operation of both receptors in rhythm generation. While NMDA alone was not able to create a rhythm, it accelerated bursting in the presence of disinhibition, made it more regular and slowed down network recruitment. These effects were most likely due to the depolarization of the interneurons in the network. We conclude that NMDA-R contribute to rhythm generation in spinal cultures by supporting recurrent excitation and network recruitment and by depolarizing the network. 相似文献
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Predictive Factors for Recurrence from a Series of 74 Children and Adolescents with Differentiated Thyroid Cancer 总被引:3,自引:0,他引:3
Borson-Chazot F Causeret S Lifante JC Augros M Berger N Peix JL 《World journal of surgery》2004,28(11):1088-1092
The influence of clinical and treatment factors on the risk of recurrence was analyzed from a retrospective series of 74 children and adolescents with thyroid cancer (55 girls, 19 boys; age 2–20 years). Two groups, comparable in terms of age, sex, and previous radiotherapy, were compared according to the presence (group 1) or absence (group 2) of cervical lymph nodes identified by palpation or ultrasonography. Total thyroidectomy (TT) with lymph node dissection (LND) was performed in the 19 group 1 patients, whereas in group 2 patients (n = 55) lobectomy was performed in 29, TT in 26, and LND in 7. Pathology studies showed papillary thyroid carcinoma in 95% of cases. In group 1, tumors were more frequently multifocal (89% vs. 16% in group 2), invasive with extension beyond the thyroid capsule (68% vs. 5% in group 2), and of the diffuse sclerosing variety (63% vs. 4% in group 2) (p < 0.001). With a median follow-up of 61 months, lymph node recurrence was seen in 53% of group 1 patients and in no patients in group 2. Three group 2 patients (10%) were reoperated for a local recurrence after lobectomy. Risk factors for reintervention were young age (< 15 years) (p < 0.01) and cervical lymph nodes (p < 0.001). Survivals without reintervention at 5 and 10 years were, respectively, 58% and 38% for group 1 and 94% and 90% for group 2 (p < 0.001). At the time of analysis, 68% of group 1 patients and 98% of group 2 patients were in remission. In conclusion, the presence of palpable cervical lymph nodes at diagnosis is associated with more invasive forms of malignancy and is a predictive factor of recurrence regardless of the extent of the initial surgery.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004. 相似文献
997.
Bombesin stimulates invasion and migration of Isreco1 colon carcinoma cells in a Rho-dependent manner 总被引:1,自引:0,他引:1
Saurin JC Fallavier M Sordat B Gevrey JC Chayvialle JA Abello J 《Cancer research》2002,62(16):4829-4835
The membrane receptor for the neuropeptide bombesin/gastrin-releasing peptide (GRP) is expressed by a large fraction of human colorectal carcinoma cells. We reported previously a stimulation of cell adhesion and lamellipodia formation by the neuropeptide bombesin in the human, bombesin/GRP receptor-expressing, Isreco1 colorectal cancer cell line (J. C. Saurin et al., Cancer Res., 59: 962-967, 1999). Using invasion and motility assays, we demonstrate in this report that bombesin can both enhance the invasive capacity of Isreco1 cells in a dose-dependent manner (maximal effect at 1 nM) and stimulate the closure of wounds performed on confluent Isreco1 cells. These effects were reversed fully by the specific bombesin/GRP receptor antagonist D-Phe(6)-Bn(6-13)OMe used at 1 micro M. MMP-9 and urokinase-type plasminogen activator were expressed by Isreco1 cells, and bombesin did not significantly alter their level of secretion. Interestingly, exoenzyme C3 (10 micro g/ml) decreased cell invasiveness induced by bombesin by 70% and completely inhibited the migration of Isreco1 cells. Similarly, the Rho-kinase inhibitor Y-27632 dose-dependently reduced the effect of bombesin on cell invasion. Moreover, pull-down assays for GTP-bound RhoA demonstrated that bombesin was able to activate the small G-protein in Isreco1 cells. These results show that the neuropeptide bombesin is able to modulate invasiveness of Isreco1 colorectal carcinoma cells in vitro through a Rho-dependent pathway, leading to an increase in cell locomotion without a significant effect on tumor-cell associated proteolytic activity. These findings indicate that bombesin/GRP receptor expression may contribute to the cellular events that are critical for invasion/migration of colorectal carcinoma cells. 相似文献
998.
Julie Mamet Julie Peyronnet Jean-Christophe Roux David Perrin Jean-Marie Cottet-Emard Jean-Marc Pequignot Hugo Lagercrantz Yvette Dalmaz 《Pediatric research》2002,51(2):207-214
Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation. A number of pathologic situations are characterized by oxygen deficiency. The objective of the present study was to determine the influence of long-term prenatal hypoxia on maturation of the adrenal medulla. Pregnant rats were subjected to hypoxia (10% O2) from the fifth to the 20th d of gestation. The offspring were examined on the 19th d of gestation (E19), the day of birth (P0), and at postnatal (P) day of life P3, P7, P14, P21, and P68. The catecholamine content and activity of tyrosine hydroxylase (TH) in vivo were assayed by HPLC with electrochemical detection. Cellular expression of TH and phenylethanolamine N-methyl transferase was evaluated by protein immunohistochemistry and in situ hybridization of the corresponding mRNA species. Exposure to prenatal hypoxia reduced the epinephrine content of the adrenal medulla on E19, P0, P3, and P7 while increasing the norepinephrine content on E19, P0, and P14. Furthermore, the peak epinephrine to norepinephrine ratio appearing between P7 and P10 in the normoxic offspring was absent in the hypoxic offspring. The in vivo TH activity was increased on P3 and P14 and decreased on P68. The percentage of chromaffin cells in the medulla expressing TH and phenylethanolamine N-methyl transferase was lowered on E19, P0, and P7. TH and phenylethanolamine N-methyl transferase mRNA levels were reduced on P7. Clearly prenatal hypoxia results in major changes in adrenal catecholamine stores and synthesis during the perinatal period, which persist into adulthood. The capacity to cope with postnatal stress might be disturbed as a consequence of prenatal hypoxia. 相似文献
999.
Induction of adiponectin in skeletal muscle by inflammatory cytokines: in vivo and in vitro studies 总被引:5,自引:0,他引:5
Adiponectin (ApN) is an adipocytokine that plays a fundamental role in energy homeostasis and counteracting inflammation. We examined whether ApN could be induced in a nonadipose tissue, the skeletal muscle, in vivo, and in cultured myotubes in response to lipopolysaccharides or proinflammatory cytokines. We next explored the underlying mechanisms. In vivo, injection of lipopolysaccharides to mice caused, after 24 h, an approximately 10-fold rise in ApN mRNA abundance and a concomitant 70% increase in ApN levels in tibialis anterior muscle. This ApN induction was reproduced in C2C12 myotubes cultured for 48 h with a proinflammatory cytokine combination, interferon-gamma + TNFalpha. This effect occurred in a time- and dose-dependent manner. Several pieces of evidence suggest that nitric oxide (NO) mediates this up-regulation by cytokines in myotubes or muscle. First, ApN was induced in vitro exclusively in the experimental conditions that stimulated NO production. Second, inducible NO synthase mRNA induction or NO production clearly preceded ApN mRNA induction. Third, preventing NO production by inhibitors of the NO synthases, nitro-L-arginine methyl ester or NG-methyl-L-arginine, suppressed the inductive effect of the cytokines in vitro and in vivo. Finally, ApN mRNA induction by cytokines was reproduced in cultured human myotubes. In conclusion, our data provide evidence that adiponectin is up-regulated in vivo and in vitro in human and rodent myotubes in response to inflammatory stimuli. The underlying mechanisms seem to involve a NO-dependent pathway. This overexpression may be viewed as a local antiinflammatory protection and a way to deliver extra energy supplies during inflammation. 相似文献
1000.