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991.
992.
Nielsen FS Gibault E Ljusberg-Wahren H Arleth L Pedersen JS Müllertz A 《Journal of pharmaceutical sciences》2007,96(4):876-892
This study describes the evaluation and characterization of a self-nanoemulsifying drug delivery system (SNEDDS) consisting of a nonionic surfactant (Cremophor RH40), a mixture of long chain mono-, di-, and triacylglycerides (Maisine 35-1 and Sesame oil) and ethanol. Compositions containing 10% (w/w) ethanol, 40%-60% (w/w) lipid content, and 30%-50% (w/w) Cremophor RH40 were identified as pharmaceutically relevant, robust, and self-nanoemulsifying when dispersed in aqueous media. The influence of adding three different lipophilic model drug compounds (danazol, halofantrine, and probucol) to the SNEDDS was evaluated. While danazol precipitated from the SNEDDS after dispersion in aqueous media, halofantrine and procubol remained solubilized. Halofantrine- and procubol-loaded SNEDDS were evaluated in both saline and in media simulating fasted and fed-state intestinal fluid (FaSSIF and FeSSIF) using dynamic light scattering and small-angle X-ray scattering (SAXS) techniques. Stable nanoemulsions with droplet sizes in the range of 20-50 nm were formed in all media and with and without drugs. The mean size of the droplets was neither affected significantly by being dispersed into the media simulating gastro intestinal fluid, nor by addition of the drug. 相似文献
993.
Adjuvant analgesics represent a diverse group of drugs that were originally developed for a primary indication other than pain. Many of these medications are currently used to enhance analgesia under specific circumstances. The proper use of adjuvant drugs is one of the keys to success in effective pain management. Since adjuvant analgesics are typically administered to patients who take multiple medications, decisions regarding administration and dosage must be made with a clear understanding of the stage of the disease and the goals of care. The article discusses major classes of adjuvant analgesics, with the focus on the mechanism of action, clinical application, and risks and benefits associated with each particular class of adjuvants. 相似文献
994.
Greenhough A Patsos HA Williams AC Paraskeva C 《International journal of cancer. Journal international du cancer》2007,121(10):2172-2180
Deregulation of cell survival pathways and resistance to apoptosis are widely accepted to be fundamental aspects of tumorigenesis. As in many tumours, the aberrant growth and survival of colorectal tumour cells is dependent upon a small number of highly activated signalling pathways, the inhibition of which elicits potent growth inhibitory or apoptotic responses in tumour cells. Accordingly, there is considerable interest in therapeutics that can modulate survival signalling pathways and target cancer cells for death. There is emerging evidence that cannabinoids, especially Delta(9)-tetrahydrocannabinol (THC), may represent novel anticancer agents, due to their ability to regulate signalling pathways critical for cell growth and survival. Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells. THC-induced apoptosis was rescued by pharmacological blockade of the CB1, but not CB2, cannabinoid receptor. Importantly, THC treatment resulted in CB1-mediated inhibition of both RAS-MAPK/ERK and PI3K-AKT survival signalling cascades; two key cell survival pathways frequently deregulated in colorectal tumours. The inhibition of ERK and AKT activity by THC was accompanied by activation of the proapoptotic BCL-2 family member BAD. Reduction of BAD protein expression by RNA interference rescued colorectal cancer cells from THC-induced apoptosis. These data suggest an important role for CB1 receptors and BAD in the regulation of apoptosis in colorectal cancer cells. The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy. 相似文献
995.
Roela RA Carraro DM Brentani HP Kaiano JH Simão DF Guarnieiro R Lopes LF Borojevic R Brentani MM 《Leukemia research》2007,31(5):579-589
Using cDNA microarray assays we have observed a clear difference in the gene expression pattern between bone marrow stromal cells obtained from healthy children (CT) and from pediatric patients with either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) associated with MDS (MDS-AML). The global gene function profiling analysis indicated that in the pediatric MDS microenvironment the disease stages may be characterized mainly by underexpression of genes associated with biological processes such as transport. Furthermore, a subset of downregulated genes related to endocytosis and protein secretion was able to discriminate MDS from MDS-AML. 相似文献
996.
Costa S Pinto D Pereira D Rodrigues H Cameselle-Teijeiro J Medeiros R Schmitt F 《Breast cancer research and treatment》2007,103(2):209-217
The purpose of this study was to evaluate the role of polymorphisms in DNA repair genes as genetic indicators of susceptibility
to familial and sporadic breast cancer. We analysed DNA samples from 285 breast cancer patients and 442 control subjects,
for XRCC1
Arg399Gln, XPD
Lys751Gln, RAD51
G135C and XRCC3
Thr241Met polymorphisms using PCR-RFLP. We observed that women carriers of XRCC1
399Gln genotypes and without family history of breast cancer have a protective effect concerning this disease (OR = 0.54 95% CI
0.35–0.84; p = 0.006). Furthermore, we found that carriers of XRCC3
241Met genotypes without FH have an increased susceptibility of breast cancer (OR = 2.21 95% CI 1.42–3.44; p < 0.001). Additionally, we verified an increased risk of breast cancer in women with FH and carrying RAD51
135C genotypes (OR = 2.17 95% CI 1.19–3.98; p = 0.012). Our results suggest XRCC1
Arg399Gln and XRCC3
Thr241Met DNA repair polymorphisms as important biomarkers to sporadic breast cancer susceptibility, as well as, RAD51
G135C polymorphism as a real risk modifier in familial breast cancer cases. 相似文献
997.
998.
The proliferation-differentiation behaviour of human alveolar bone cell cultures grown for 32 days in conditions that allowed the complete expression of the osteoblastic phenotype was significantly affected by the continuous presence of parathyroid hormone, 1, 25-dihydroxyvitamin D(3), or dexamethasone. Parathyroid hormone and, in particular, dexamethasone significantly induced the differentiation of osteoblastic cells. Moreover, cultures exposed to these hormones presented an earlier appearance and higher levels of alkaline phosphatase, and an increased ability to form calcium phosphate deposits in the extracellular matrix. 相似文献
999.
Helena Rexius Folke Nilsson Anders Jeppsson 《Scandinavian cardiovascular journal : SCJ》2013,47(6):342-344
An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed. 相似文献
1000.