全文获取类型
收费全文 | 1639篇 |
免费 | 122篇 |
国内免费 | 25篇 |
专业分类
儿科学 | 146篇 |
妇产科学 | 31篇 |
基础医学 | 164篇 |
口腔科学 | 67篇 |
临床医学 | 160篇 |
内科学 | 365篇 |
皮肤病学 | 41篇 |
神经病学 | 41篇 |
特种医学 | 331篇 |
外科学 | 100篇 |
综合类 | 24篇 |
预防医学 | 79篇 |
眼科学 | 16篇 |
药学 | 104篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 115篇 |
出版年
2022年 | 5篇 |
2021年 | 20篇 |
2020年 | 13篇 |
2019年 | 12篇 |
2018年 | 25篇 |
2017年 | 17篇 |
2016年 | 24篇 |
2015年 | 34篇 |
2014年 | 27篇 |
2013年 | 51篇 |
2012年 | 13篇 |
2011年 | 17篇 |
2010年 | 42篇 |
2009年 | 81篇 |
2008年 | 27篇 |
2007年 | 44篇 |
2006年 | 45篇 |
2005年 | 37篇 |
2004年 | 21篇 |
2003年 | 27篇 |
2002年 | 25篇 |
2001年 | 27篇 |
2000年 | 26篇 |
1999年 | 34篇 |
1998年 | 102篇 |
1997年 | 119篇 |
1996年 | 112篇 |
1995年 | 77篇 |
1994年 | 82篇 |
1993年 | 98篇 |
1992年 | 21篇 |
1991年 | 21篇 |
1990年 | 25篇 |
1989年 | 51篇 |
1988年 | 41篇 |
1987年 | 29篇 |
1986年 | 38篇 |
1985年 | 43篇 |
1984年 | 22篇 |
1983年 | 18篇 |
1982年 | 20篇 |
1981年 | 35篇 |
1980年 | 22篇 |
1979年 | 16篇 |
1978年 | 8篇 |
1977年 | 24篇 |
1976年 | 21篇 |
1975年 | 8篇 |
1970年 | 6篇 |
1961年 | 4篇 |
排序方式: 共有1786条查询结果,搜索用时 15 毫秒
201.
The authors present two cases of percutaneous cecostomy performed with a modified approach previously described for percutaneous gastrostomy and cholecystostomy. T-fastener devices were used to affix the cecum to the anterior abdominal wall; thus, the potential problem of fecal spillage was prevented. In both cases, adequate fecal drainage was provided without complication. 相似文献
202.
Obrosova IG Fathallah L Stevens MJ 《Journal of the peripheral nervous system : JPNS》2002,7(2):134-135
Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin‐diabetic rats fed standard or 1% T‐supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4‐hydroxyalkenals (4‐HA) were quantified with N‐methyl‐2‐phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse‐phase HPLC, and NGF by ELISA. MDA plus 4‐HA concentration (mean +/? SEM) was increased in diabetic rats (0.127 +/?0.006 vs 0.053 +/?0.003 mu mol/g in controls, P<0.01), and this increase was partially prevented by T (0.0960.004, P<0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P<0.05 vs controls). AA levels were decreased in diabetic rats (0.133+0.015 vs 0.219 +/?0.023 mu mol/g in controls, P<0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P<0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/?0.16 vs 3.8 +/?0.1 mu mol/g in controls, P<0.05) and were repleted by T supplementation (4.20.3). NGF levels were decreased in diabetic rats (2.35 +/?0.20 vs 3.57 +/?0.20 ng/g in controls, P<0.01), and this decrease was attenuated by T treatment (3.160.28, P<0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN. 相似文献
203.
C Pina-Vaz†‡§ A Gonçalves Rodrigues†‡§ E Pinto¶ S Costa-de-Oliveira† C Tavares† L Salgueiro†† C Cavaleiro†† MJ Gonçalves†† J Martinez-de-Oliveira§ 《Journal of the European Academy of Dermatology and Venereology》2004,18(1):73-78
The increasing recognition and importance of fungal infections, the difficulties encountered in their treatment and the increase in resistance to antifungals have stimulated the search for therapeutic alternatives. Essential oils have been used empirically. The essential oils of Thymus (Thymus vulgaris, T. zygis subspecies zygis and T. mastichina subspecies mastichina) have often been used in folk medicine. The aim of the present study was to evaluate objectively the antifungal activity of Thymus oils according to classical bacteriological methodologies - determination of the minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) - as well as flow cytometric evaluation. The effect of essential oils upon germ tube formation, an important virulence factor, was also studied. The mechanism of action was studied by flow cytometry, after staining with propidium iodide. The chemical composition of the essential oils was investigated by gas chromatography (GC) and gas chromatography/mass spectroscopy (GC/MS). The antifungal activity of the major components (carvacrol, thymol, p-cymene and 1,8-cineole) and also possible interactions between them were also investigated. The essential oils of T. vulgaris and T. zygis showed similar antifungal activity, which was greater than T. mastichina. MIC and MLC values were similar for all the compounds tested. At MIC values of the essential oils, propidium iodide rapidly penetrated the majority of the yeast cells, indicating that the fungicidal effect resulted primarily from an extensive lesion of the cell membrane. Concentrations below the MIC values significantly inhibited germ tube formation. This study describes the potent antifungal activity of the essential oils of Thymus on Candida spp., warranting future therapeutical trials on mucocutaneous candidosis. 相似文献
204.
Efficacy study of the small-bowel examination 总被引:8,自引:0,他引:8
205.
We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA- binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA- binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma. 相似文献
206.
207.
Clonal rearrangements of the Ig heavy chain (IGH) locus occur in nearly all cases of B-cell precursor acute leukemia (BCP-ALL). Some of these rearrangements may be detected by polymerase chain reaction (PCR) using VH gene framework III (FRIII) and JH consensus primers. However, about 20% of BCP-ALLs fail to amplify with this technique. To determine the causes of these PCR failures and to investigate any possible association with specific subgroups of disease, we analyzed 72 acute leukemias of defined immunophenotype and cytogenetics, comparing FRIII with VH-family leader-specific PCR methods and Southern blotting. Of 37 BCP-ALL cases, 6 (16.2%) failed totally to amplify with FRIII and JH primers. None of these cases amplified with VH leader primers. Additionally, all cases retained germline VH6 genes and 5 of 11 rearranged alleles amplified with a consensus DH primer, indicating that these rearrangements represented biallelic DH-JH recombinations. Among the 6 FRIII and VH leader PCR-negative BCP-ALL cases, there was no common immunophenotype or consistent cytogenetic abnormality, although all showed structural chromosomal abnormalities and 3 of 5 successfully karyotyped had abnormalities of chromosome 12p. 13 cases with t(9;22)(q34;q11) Philadelphia chromosome-positive [Ph+]) and IGH rearrangements (9 BCP-ALL and 4 biphenotypic cases) were also analyzed. Of 23 rearranged IGH alleles, 19 (82%) were positive by FRIII PCR, and all 4 remaining alleles were amplified by VH leader primers. Use of the leader primers in these Ph+ cases also detected 3 additional clonal rearrangements that were not anticipated from Southern blotting; such unexpected bands were not observed in 21 other Ph- cases. The additional bands represented "new" and unrelated VH rearrangements rather than VH-VH replacement events. We conclude that biallelic DHJH rearrangements occur in a subgroup of BCP-ALL; in these cases, the activation of the full VHDHJH recombination mechanism had not occurred. Therefore, these cases of BCP-ALL were arrested at an early stage of B- cell differentiation. In contrast, all Ph+ BCP-ALLs and biphenotypic acute leukemias, which may represent the transformation of multipotent hemopoietic stem cells, had undergone VHDHJH recombination. Of 9 Ph+ BCP-ALL cases, 3 also showed ongoing VHDHJH rearrangement, reflecting the persistent expression of the VHDHJH recombinase. Finally, sequence analysis of 33 rearranged VHDHJH genes showed that only 3 including 2 Ph+ BCP-ALL maintained an intact open-reading frame. Loss of the open- reading frame occurred not only because of out-of-frame VHDH and DHJH joining, but also because of VH gene mutation and deletion. These data show that most BCP-ALLs may represent the neoplastic transformation of BCPs destined to die in the bone marrow. 相似文献
208.
We investigated the effects of hypoxia on red blood cell (RBC)- endothelial cell (EC) adherence and the potential mechanism(s) involved in mediating this effect. We report that hypoxia significantly increased sickle RBC adherence to aortic EC when compared with the normoxia controls. However, hypoxia had no effect on the adherence of normal RBCs. In additional studies, we found that the least dense sickle RBCs containing CD36+ and VLA-4+ reticulocytes were involved in hypoxia-induced adherence. We next evaluated the effects of hypoxia on the expression of EC surface receptors involved in RBC adherence to macrovascular ECs, including vascular cell adhesion molecule-1 (VCAM- 1), intracellular adhesion molecule-1 (ICAM-1), and the vitronectin receptor (VnR). Hypoxia upregulated the expression of both VCAM-1 and ICAM-1, whereas no effect on VnR was noted. Potential involvement of VCAM-1 and ICAM-1 in mediating hypoxia-induced sickle RBC-EC adhesion was next investigated using monoclonal antibodies against these receptors. Whereas anti-VCAM-1 had no effect on basal adherence, it inhibited hypoxia-induced sickle RBC adherence in a concentration- dependent manner, with 50% to 75% inhibition noted at 10 to 60 micrograms/mL antibody (n = 6, P < .05 to P < .01). Anti-ICAM-1 (10 to 60 micrograms/mL, n = 8) had no effect on either basal or hypoxia- induced adherence. As noted in the bovine aortic ECs, hypoxia stimulated the adherence of sickle RBCs to human retinal capillary ECs, and this response appeared to be mediated via mechanisms similar to those observed with macro-endothelium, ie, via the adhesive receptor combination VCAM-1-VLA-4. Our studies show that hypoxia enhances sickle RBC adhesion to both macrovascular and human microvascular ECs via the adhesive receptor VCAM-1. Our findings are of interest because hypoxia is an integral part of the pathophysiology of the vaso-occlusive phenomenon in sickle cell anemia. 相似文献
209.
Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL. 相似文献
210.
Ross AA; Cooper BW; Lazarus HM; Mackay W; Moss TJ; Ciobanu N; Tallman MS; Kennedy MJ; Davidson NE; Sweet D 《Blood》1993,82(9):2605-2610
Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro. 相似文献