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131.
132.
Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study
Czuczman MS Fayad L Delwail V Cartron G Jacobsen E Kuliczkowski K Link BK Pinter-Brown L Radford J Hellmann A Gallop-Evans E DiRienzo CG Goldstein N Gupta I Jewell RC Lin TS Lisby S Schultz M Russell CA Hagenbeek A; Study Investigators 《Blood》2012,119(16):3698-3704
New treatments are required for rituximab-refractory follicular lymphoma (FL). In the present study, patients with rituximab-refractory FL received 8 weekly infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg; N = 116). The median age of these patients was 61 years, 47% had high-risk Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy-refractory, and the median number of prior therapies was 4. The overall response rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27 patients refractory to rituximab monotherapy, the overall response rate was 22%. The median progression-free survival was 5.8 months. Forty-six percent of patients demonstrated tumor reduction 3 months after therapy initiation, and the median progression-free survival for these patients was 9.1 months. The most common adverse events included infections, rash, urticaria, fatigue, and pruritus. Three patients experienced grade 3 infusion-related reactions, none of which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia, and thrombocytopenia occurred in a subset of patients. Ofatumumab was well tolerated and modestly active in this heavily pretreated, rituximab-refractory population and is therefore now being studied in less refractory FL and in combination with other agents in various B-cell neoplasms. The present study was registered at www.clinicaltrials.gov as NCT00394836. 相似文献
133.
134.
Krzystek-Korpacka M Diakowska D Grabowski K Gamian A 《International journal of colorectal disease》2012,27(10):1319-1324
Purpose
The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location.Methods
Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels.Results
Midkine was higher in cancerous versus noncancerous tissue in 98?% cases (424.2 vs. 31.1?pg/mg, p?0.0001). Mean fold increase was 30.1; in 72.5?%, the relative increase was over fivefold. Midkine upregulation was more pronounced in colon than in rectum (fold increase: 36.6 vs. 12.7, p?=?0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2?pg/mg, p?=?0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p?=?0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p?=?0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p?=?0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p?=?0.085). Midkine negatively correlated with tumor size (r?=?0.40, p?=?0.017), while it tended to positively correlate with its serum levels (r?=?0.45, p?=?0.081).Conclusions
Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC. 相似文献135.
136.
Kim TK Wang J Janjetovic Z Chen J Tuckey RC Nguyen MN Tang EK Miller D Li W Slominski AT 《Molecular and cellular endocrinology》2012,361(1-2):143-152
To define the interaction of novel secosteroids produced by the action of cytochrome P450scc with vitamin D receptor (VDR), we used a human melanoma line overexpressing VDR fused with enhanced green fluorescent protein (EGFP) and tested the ligand induced translocation of VDR from the cytoplasm to the nucleus. Hydroxyderivatives of vitamin D(3) with a full length (D(3)) side chain and hydroxy-secosteroids with a shortened side chain (pD) stimulated VDR translocation and inhibited proliferation, however, with different potencies. In general the D(3) were more potent than pD analogues. Molecular modeling of the binding of the secosteroids to the VDR genomic binding pocket (G-pocket) correlated well with the experimental data for VDR translocation. In contrast, docking scores for the non-genomic binding site of the VDR were poor. In conclusion, both the length of the side chain and the number and position of hydroxyl groups affect the activation of VDR by novel secosteroids. 相似文献
137.
Slominski RM Reiter RJ Schlabritz-Loutsevitch N Ostrom RS Slominski AT 《Molecular and cellular endocrinology》2012,351(2):152-166
Many of melatonin's actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes. 相似文献
138.
Bartke A 《Gerontology》2012,58(4):337-343
A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth. 相似文献
139.
Aleksandra Bala Szczepan Iwański Jarosław Żyłkowski Maciej Jaworski Joanna Seniów Andrzej Marchel 《Neurocase》2013,19(3):331-338
Presented case report illustrates symptoms of prosopometamorphopsia (PM) and prosopagnosia, observed in the early days after the onset of a hemorrhagic stroke resulting from a complication of endovascular treatment of intracranial aneurysms and the use of anticoagulation therapy. PM is a visual disorder in which faces are perceived as distorted. The female patient described in the present study reported that faces she looked at seemed younger or older than in reality or as if they were dirty, swollen, or with a grimace. She also experienced symptoms of prosopagnosia, which is difficulty of recognizing familiar faces of people (e.g., of her husband and daughter). In the interview 6 months after the first examination, the patient reported spontaneous withdrawal of the visual disturbances. 相似文献
140.
Andrzej Jamry Marek Ja?yński ?ukasz Piskorz Marian Brocki 《Archives of Medical Science》2013,9(3):487-492