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91.
92.
Marco Seandel Jason M. Butler Hideki Kobayashi Andrea T. Hooper Ian A. White Fan Zhang Eva L. Vertes Mariko Kobayashi Yan Zhang Sergey V. Shmelkov Neil R. Hackett Sina Rabbany Julie L. Boyer Shahin Rafii 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(49):19288-19293
Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates organ-specific purification of PECs, while preserving their vascular repertoire for months, in serum/cytokine-free cultures. Lentiviral introduction of E4ORF1 into human PECs (E4ORF1+ ECs) increased the long-term survival of these cells in serum/cytokine-free conditions, while preserving their in vivo angiogenic potential for tubulogenesis and sprouting. Although E4ORF1, in the absence of mitogenic signals, does not induce proliferation of ECs, stimulation with VEGF-A and/or FGF-2 induced expansion of E4ORF1+ ECs in a contact-inhibited manner. Indeed, VEGF-A-induced phospho MAPK activation of E4ORF1+ ECs is comparable with that of naive PECs, suggesting that the VEGF receptors remain functional upon E4ORF1 introduction. E4ORF1+ ECs inoculated in implanted Matrigel plugs formed functional, patent, humanized microvessels that connected to the murine circulation. E4ORF1+ ECs also incorporated into neo-vessels of human tumor xenotransplants and supported serum/cytokine-free expansion of leukemic and embryonal carcinoma cells. E4ORF1 augments survival of PECs in part by maintaining FGF-2/FGF-R1 signaling and through tonic Ser-473 phosphorylation of Akt, thereby activating the mTOR and NF-κB pathways. Therefore, E4ORF1+ ECs establish an Akt-dependent durable vascular niche not only for expanding stem and tumor cells but also for interrogating the roles of vascular cells in regulating organ-specific vascularization and tumor neo-angiogenesis. 相似文献
93.
A Klar N Livni E Gross-Kieselstein P Navon A Shahin D Branski 《Archives of pathology & laboratory medicine》1987,111(2):197-199
We present the results of light and electron microscopy studies of the liver in an 8-year-old girl with congenital total lipodystrophy. Liver histology revealed cirrhosis, and ultrastructural study showed mitochondrial abnormalities and an increase in the number of peroxisomes. A potential relationship between the high fatty acid concentration in the serum and the peroxisomal proliferation is considered. 相似文献
94.
CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes 下载免费PDF全文
Chitsazian F Tusi BK Elahi E Saroei HA Sanati MH Yazdani S Pakravan M Nilforooshan N Eslami Y Mehrjerdi MA Zareei R Jabbarvand M Abdolahi A Lasheyee AR Etemadi A Bayat B Sadeghi M Banoei MM Ghafarzadeh B Rohani MR Rismanchian A Thorstenson Y Sarfarazi M 《The Journal of molecular diagnostics : JMD》2007,9(3):382-393
The mutation spectrum of CYP1B1 among 104 primary congenital glaucoma patients of the genetically heterogeneous Iranian population was investigated by sequencing. We also determined intragenic single nucleotide polymorphism (SNP) haplotypes associated with the mutations and compared these with haplotypes of other populations. Finally, the frequency distribution of the haplotypes was compared among primary congenital glaucoma patients with and without CYP1B1 mutations and normal controls. Genotype classification of six high-frequency SNPs was performed using the PHASE 2.0 software. CYP1B1 mutations in the Iranian patients were very heterogeneous. Nineteen nonconservative mutations associated with disease, and 10 variations not associated with disease were identified. Ten mutations and three variations not associated with disease were novel. The 13 novel variations make a notable contribution to the approximately 70 known variations in the gene. CYP1B1 mutations were identified in 70% of the patients. The four most common mutations were G61E, R368H, R390H, and R469W, which together constituted 76.2% of the CYP1B1 mutated alleles found. Six unique core SNP haplotypes were identified, four of which were common to the patients with and without CYP1B1 mutations and controls studied. Three SNP blocks determined the haplotypes. Comparison of haplotypes with those of other populations suggests a common origin for many of the mutations. 相似文献
95.
96.
Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors 总被引:1,自引:0,他引:1
Kermani P Rafii D Jin DK Whitlock P Schaffer W Chiang A Vincent L Friedrich M Shido K Hackett NR Crystal RG Rafii S Hempstead BL 《The Journal of clinical investigation》2005,115(3):653-663
The neurotrophin brain-derived neurotrophic factor (BDNF) is required for the maintenance of cardiac vessel wall stability during embryonic development through direct angiogenic actions on endothelial cells expressing the tropomysin receptor kinase B (TrkB). However, the role of BDNF and a related neurotrophin ligand, neurotrophin-4 (NT-4), in the regulation of revascularization of the adult tissues is unknown. To study the potential angiogenic capacity of BDNF in mediating the neovascularization of ischemic and non-ischemic adult mouse tissues, we utilized a hindlimb ischemia and a subcutaneous Matrigel model. Recruitment of endothelial cells and promotion of channel formation within the Matrigel plug by BDNF and NT-4 was comparable to that induced by VEGF-A. The introduction of BDNF into non-ischemic ears or ischemic limbs induced neoangiogenesis, with a 2-fold increase in the capillary density. Remarkably, treatment with BDNF progressively increased blood flow in the ischemic limb over 21 days, similar to treatment with VEGF-A. The mechanism by which BDNF enhances capillary formation is mediated in part through local activation of the TrkB receptor and also by recruitment of Sca-1+CD11b+ pro-angiogenic hematopoietic cells. BDNF induces a potent direct chemokinetic action on subsets of marrow-derived Sca-1+ hematopoietic cells co-expressing TrkB. These studies suggest that local regional delivery of BDNF may provide a novel mechanism for inducing neoangiogenesis through both direct actions on local TrkB-expressing endothelial cells in skeletal muscle and recruitment of specific subsets of TrkB+ bone marrow-derived hematopoietic cells to provide peri-endothelial support for the newly formed vessels. 相似文献
97.
Chemotherapy- or radiation-induced myelosuppression results in apoptosis of cycling hematopoietic cells and induces regression of bone marrow (BM) sinusoidal vessels. Moreover, timely regeneration of BM neovessels is essential for reconstitution of hematopoiesis. However, the identity of angiogenic factors that support reconstitution of BM's vasculature is unknown. Here, we demonstrate that angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (Tie2) signaling contributes to the assembly and remodeling of BM neovessels after myelosuppression. Using transgenic mice where the Tie2 promoter drives the reporter LacZ gene (Tie2-LacZ), we demonstrate that at steady state, there was minimal expression of Tie2 in the BM vasculature. However, after 5-fluorouracil (5-FU) treatment, there was a rapid increase in plasma vascular endothelial growth factor A (VEGF-A) levels and expansion of Tie2-positive neovessels. Inhibition of Tie2 resulted in impaired neoangiogenesis, leading to a delay in hematopoietic recovery. Conversely, angiopoietin-1 (Ang-1) stimulated hematopoiesis both in wild-type and thrombopoietin-deficient mice. In addition, Ang-1 shortened the duration of chemotherapy-induced neutropenia in wild-type mice. Exogenous VEGF-A and Ang-1 stimulated Tie2 expression in the BM vasculature. These data suggest that VEGF-A-induced up-regulation of Tie2 expression on the regenerating vasculature after BM suppression supports the assembly of sinusoidal endothelial cells, thereby promoting reconstitution of hematopoiesis. Angiopoietins may be clinically useful to accelerate hemangiogenic recovery after myelosuppression. 相似文献
98.
Farshad Arsalandeh Fariba Khodagholi Shahin Ahmadian Forough Foolad Hamed Mohammadi Kamsorkh Mahdi Moridi Farimani 《Nutritional neuroscience》2019,22(4):295-301
Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4?-trimethoxyflavone (flavone 1) and 5,7,4?-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aβ-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protein-1 protein level, a known marker for mitochondrial fission, and elevation in protein level of mitochondrial fusion factors Mitofusins 1 and 2. In parallel with behavior results, flavone 1 was more effectual on mitochondrial dynamic moderating. The more neuroprotective effects of flavone 1 could be attributed to its methylated structure leading to crossing of the blood-brain barrier with ease and metabolic stability and bioactivity. 相似文献
99.
Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol 总被引:3,自引:0,他引:3
Merat S Aduli M Kazemi R Sotoudeh M Sedighi N Sohrabi M Malekzadeh R 《Digestive diseases and sciences》2008,53(8):2246-2250
BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment. 相似文献
100.
Shahin Merat Shadi Khalili Pardise Mostajabi Anahita Ghorbani Reza Ansari Reza Malekzadeh 《Digestive diseases and sciences》2010,55(5):1385-1390
Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome
(IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule
of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients
after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from
abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore,
Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and
safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort. 相似文献