全文获取类型
收费全文 | 1306篇 |
免费 | 129篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 85篇 |
妇产科学 | 34篇 |
基础医学 | 173篇 |
口腔科学 | 23篇 |
临床医学 | 133篇 |
内科学 | 236篇 |
皮肤病学 | 26篇 |
神经病学 | 113篇 |
特种医学 | 59篇 |
外科学 | 204篇 |
综合类 | 51篇 |
预防医学 | 165篇 |
眼科学 | 10篇 |
药学 | 83篇 |
中国医学 | 4篇 |
肿瘤学 | 48篇 |
出版年
2022年 | 6篇 |
2021年 | 20篇 |
2020年 | 7篇 |
2019年 | 19篇 |
2018年 | 24篇 |
2017年 | 31篇 |
2016年 | 18篇 |
2015年 | 34篇 |
2014年 | 44篇 |
2013年 | 44篇 |
2012年 | 77篇 |
2011年 | 46篇 |
2010年 | 40篇 |
2009年 | 54篇 |
2008年 | 52篇 |
2007年 | 59篇 |
2006年 | 47篇 |
2005年 | 62篇 |
2004年 | 31篇 |
2003年 | 33篇 |
2002年 | 40篇 |
2001年 | 57篇 |
2000年 | 51篇 |
1999年 | 37篇 |
1998年 | 45篇 |
1997年 | 41篇 |
1996年 | 21篇 |
1995年 | 30篇 |
1994年 | 23篇 |
1993年 | 26篇 |
1992年 | 25篇 |
1991年 | 22篇 |
1990年 | 15篇 |
1989年 | 25篇 |
1988年 | 12篇 |
1987年 | 19篇 |
1986年 | 18篇 |
1985年 | 18篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 12篇 |
1981年 | 14篇 |
1980年 | 9篇 |
1979年 | 9篇 |
1976年 | 8篇 |
1975年 | 6篇 |
1972年 | 8篇 |
1971年 | 8篇 |
1967年 | 9篇 |
1965年 | 7篇 |
排序方式: 共有1452条查询结果,搜索用时 15 毫秒
51.
Anna Porter Michael J. Fischer Xuelei Wang Deborah Brooks Marino Bruce Jeanne Charleston William H. Cleveland Donna Dowie Marquetta Faulkner Jennifer Gassman Leena Hiremath Cindy Kendrick John W. Kusek Keith C. Norris Denyse Thornley-Brown Tom Greene James P. Lash 《Journal of the American Society of Nephrology : JASN》2014,25(8):1849-1855
Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD. 相似文献
52.
53.
Grigg AP; Roberts AW; Raunow H; Houghton S; Layton JE; Boyd AW; McGrath KM; Maher D 《Blood》1995,86(12):4437-4445
To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients. 相似文献
54.
The activation of factor XI initiates the intrinsic coagulation pathway. Until recently it was believed that the main activator of factor XI is factor XIIa in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface. Two recent reports have presented evidence that in a purified system factor XI is activatable by thrombin together with the soluble polyanion dextran sulfate. To assess the physiological relevance of these findings we studied the activation of factor XI in normal and factor XII-deficient plasma. We used either kaolin/cephalin or dextran sulfate as a surface for the intrinsic coagulation pathway, tissue factor to generate thrombin via the extrinsic pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is rapidly cleaved on incubation with kaolin. The kinetics appear to be exponential with half the maximum cleavage at 5 minutes. Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. Tissue factor (1:500) added to plasma did not induce cleavage of factor XI during a 90-minute incubation, although fibrin formation within 30 seconds indicated that thrombin was generated via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to 50% prothrombin activation) directly to factor XII deficient or normal plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to instantaneous fibrinogen cleavage, but again no cleavage of factor XI was observable. We conclude that in plasma surroundings factor XI is not activated by thrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable. 相似文献
55.
The regulation of myelopoiesis was evaluated in B6D2F1 mice inoculated with Friend virus complex (spleen focus-forming virus plus helper virus) or helper virus alone by analyzing acidic isoferritin (AIF) and lactoferrin (LF) interactions with target cells. Under normal conditions, AIF suppresses colony and cluster formation by an Ia- antigen-positive cycling subpopulation of mouse granulocyte-macrophage progenitor cells (CFU-GM). Under the same conditions, the release of AIF-inhibitory activity and granulocyte-macrophage colony stimulatory factors (GM-CSF) from an Ia-antigen-positive subpopulation of monocytes and macrophages is suppressed by LF. Within one to two days after inoculation in vivo with Friend virus complex or helper virus, mouse CFU-GM become insensitive in vitro to suppression by purified human AIF as well as crude mouse AIF, and by four days, bone marrow, spleen, and thymus cells of these mice release much greater quantities of AIF- inhibitory activity than the cells from mice injected with control medium. The Friend virus complex itself has no influence in vitro on CFU-GM from normal mice. In addition, the release of AIF-inhibitory activity from bone marrow, spleen, and resident peritoneal cells and the release of GM-CSF from resident peritoneal cells of mice infected with Friend virus complex are not suppressed by LF. The inability of AIF to suppress colony formation by bone marrow and spleen CFU-GM from mice infected with Friend virus complex is associated with the loss of Ia (I-A subregion) antigens from CFU-GM, even though CFU-GM are in cycle. The nonresponsiveness of bone marrow, spleen, and peritoneal cells from these mice to LF suppression of AIF release and the inability of LF to influence GM-CSF release from peritoneal cells is associated with loss of Ia antigens from these cells. The above abnormalities are similar to the defects noted using cells from patients with leukemia. These results suggest that mice infected with Friend virus complex can serve as a model for investigating abnormalities in cell regulation and their relationships to disease progression. 相似文献
56.
O'Malley CJ; Rasko JE; Basser RL; McGrath KM; Cebon J; Grigg AP; Hopkins W; Cohen B; O'Byrne J; Green MD; Fox RM; Berndt MC; Begley CG 《Blood》1996,88(9):3288-3298
This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status. 相似文献
57.
I. S. Mann L. Froschauer H. P. Parkman S. Harbison T. L. Abell W. J. Snape W. L. Hasler R. W. McCallum I. Sarosiek L. A. B. Nguyen K. L. Koch J. Tonascia F. A. Hamilton M. L. Kendrick K. R. Shen P. J. Pasricha G. Farrugia the NIDDK Gastroparesis Clinical Research Consortium 《Neurogastroenterology and motility》2014,26(9):1275-1284
58.
Steven Masson Benjamin Marrow Stuart Kendrick Ahmed M. Elsharkawy Sandra Latimer Mark Hudson 《Transplant international》2014,27(5):475-481
Return to drinking after liver transplantation for alcoholic liver disease (ALD) remains a source of unease with varying reported rates of return to drinking and impact this has on graft function. In 2005, the UK Transplant liver advisory group recommended an ‘alcohol contract’ in which ALD patients listed for transplantation confirmed in writing their commitment to abstinence. We aimed to measure the rates and consequences of return to drinking alcohol in a UK transplant programme and assess the effect of the ‘alcohol contract’. Consecutive patients transplanted for ALD during 1996–2011 were included. Every patient listed after Feb 2007 signed up to the ‘alcohol contract’. We compared rates and pattern of return to drinking and survival before and after the introduction of the contract. Overall, 52 (37%) patients returned to drinking alcohol; 37 (39%) before and 15 (34%) after the contract. There was no significant difference in the rate of return or pattern of drinking. Median survival was 176 months (145–207 95% CI). There was no significant difference in survival, mortality rates, or in the causes of death in either group. We report high rates of return to drinking alcohol in a UK liver transplant programme. Despite this, the impact on patient and graft survival is low. There is no evidence that an ‘alcohol contract’ has had any effect on alcohol consumption. 相似文献
59.
60.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its therapeutic potential in breast and gynecologic cancers 总被引:4,自引:1,他引:3
OBJECTIVE: The relationship between the apoptotic pathway and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising area of scientific interest for cancer researchers. TRAIL-receptor-activating agents have demonstrated favorable in vitro and in vivo activity for the treatment of several malignancies including breast and gynecologic cancers. METHODS: This article reviews the available peer-reviewed literature and our own institution's experience with specific TRAIL-receptor-activating agents. Emphasis was placed on the apoptotic/TRAIL mechanism, preclinical evaluation, and phase I studies in various malignancies. RESULTS: Preclinical and early phase I studies indicate that these novel agents are safe with enhanced target specificity for malignancy. When these targeted agents are combined with conventional chemotherapy drugs or radiation therapy, they appear to increase cell death over single-agent modalities. CONCLUSIONS: TRAIL-receptor-activating agents represent an exciting new class of targeted therapies that hold promise to improve the treatment of women with breast and gynecologic malignancies. 相似文献