首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2071篇
  免费   208篇
  国内免费   2篇
  2023年   14篇
  2022年   9篇
  2021年   23篇
  2020年   22篇
  2019年   21篇
  2018年   23篇
  2017年   22篇
  2016年   43篇
  2015年   98篇
  2014年   110篇
  2013年   129篇
  2012年   154篇
  2011年   158篇
  2010年   99篇
  2009年   79篇
  2008年   103篇
  2007年   88篇
  2006年   125篇
  2005年   92篇
  2004年   88篇
  2003年   74篇
  2002年   72篇
  2001年   60篇
  2000年   67篇
  1999年   55篇
  1998年   15篇
  1997年   20篇
  1996年   12篇
  1995年   13篇
  1994年   14篇
  1993年   12篇
  1992年   24篇
  1991年   32篇
  1990年   13篇
  1989年   23篇
  1988年   26篇
  1987年   19篇
  1986年   31篇
  1985年   26篇
  1984年   19篇
  1983年   16篇
  1982年   8篇
  1980年   10篇
  1979年   10篇
  1978年   15篇
  1976年   14篇
  1975年   14篇
  1973年   9篇
  1972年   6篇
  1969年   6篇
排序方式: 共有2281条查询结果,搜索用时 15 毫秒
1.
2.

Objectives

To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma.

Methods

In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated.

Results

Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P < 0.001 and P = 0.001, respectively) than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis.

Conclusion

Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract urothelial carcinoma.  相似文献   
3.
LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15–30% lower circulating LDL-C and a disproportionately lower risk (47–88%) of experiencing a cardiovascular event. Here, we utilized pcsk9−/− mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9−/− mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (−45%) and TGs (−36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (−91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression.  相似文献   
4.
Striped Marlin is a highly migratory species distributed throughout tropical and temperate waters in the North Pacific Ocean. The habitat characteristics of Striped Marlin in the western and central North Pacific Ocean were examined using generalized additive models by modelling fishery catch-rates as a function of remotely-sensed environmental covariates, including sea surface temperature (SST), chlorophyll-a concentration (CHL), mixed layer depth (MLD) and sea height anomalies (SHA). SST explained the largest proportion of the deviance, and is therefore considered the best predictor for the habitat of Striped Marlin. Spatial distributions of the relative density of Striped Marlin indicated that there is a seasonal north–south migration, and that the highest densities occur in the central North Pacific Ocean. The preferred habitat characteristics of Striped Marlin in high density areas were identified as SST between 23 and 26 °C, MLD within 30 m depth, and CHL around 0.08 mg m?3, while no preferred range was found for SHA. The results of this study could improve our understanding of Striped Marlin spatial distributions and habitat characteristics.  相似文献   
5.

Background

We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.

Design of study

Case-crossover design.

Methods and Materials

Elderly enrollees (n = 6010) in Taiwan’s National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.

Results

After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.

Conclusion

Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.  相似文献   
6.
Megacrania tsudai, a peripherally distributed member of Megacrania, requires conservation in Taiwan; it has limited distribution in Taiwan and its eastern offshore islands. It feeds on screw pines (Pandanus odoratissimus) in nature and has demonstrated a specific defensive mechanism involving actinidine secretion from the prothoracic gland. However, details of its distribution area, life cycle and developmental phenology remain largely unknown. In this study, a field survey and review of published works revealed M. tsudai distribution in coastal zones and along river shores near estuaries. At room temperature, the egg period was 128 days. The development of the first to sixth instars required 17, 26, 27, 26, 34 and 43 days, respectively, on average; and a generation cycle required approximately 204 days. The phenology of the mesonotal granules was recorded. Moreover, genetic analysis of the mitochondrial cytochrome oxidase I (COI), 16S ribosomal DNA (16S rDNA) and the nuclear ribosomal spacer indicated the occurrence of genetic drift. Therefore, the rearing procedures proposed in this study for the primary and last instars of M. tsudai can facilitate its conservation. Megacrania tsudai was previously recorded as parthenogenetic; however, two male individuals were fostered unexpectedly. The male body length was 91 mm, which is shorter than the female length (120 mm). During mating, the male climbs onto the female's back and protrudes its genitalia downward. Geographical parthenogenesis is likely the reproductive strategy among peripheral M. tsudai; however, the rarely found M. tsudai male could be an intermediate link of reproductive strategy in the transition from tychoparthenogenesis to parthenogenesis.  相似文献   
7.
Pulmonary tuberculosis (TB) is caused by Mycobacterium tuberculosis. The protein composition of sputum may reflect the immune status of the lung. This study aimed to evaluate the protein profiles in spontaneous sputum samples from patients with active pulmonary TB. Sputum samples were collected from patients with pulmonary TB and healthy controls. Western blotting was used to analyze the amount of interleukin 10 (IL-10), interferon-gamma (IFN-γ), IL-25, IL-17, perforin-1, urease, albumin, transferrin, lactoferrin, adenosine deaminase (also known as adenosine aminohydrolase, or ADA), ADA-2, granzyme B, granulysin, and caspase-1 in sputum. Results of detection of IL-10, IFN-γ, perforin-1, urease, ADA2, and caspase-1, showed relatively high specificity in distinguishing patients with TB from healthy controls, although sensitivities varied from 13.3% to 66.1%. By defining a positive result as the detection of any two proteins in sputum samples, combined use of transferrin and urease as markers increased sensitivity to 73.2% and specificity to 71.1%. Furthermore, we observed that the concentration of transferrin was proportional to the number of acid-fast bacilli detected in sputum specimens. Detection of sputum transferrin and urease was highly associated with pulmonary TB infection. In addition, a high concentration of transferrin detected in sputum might correlate with active TB infection. This data on sputum proteins in patients with TB may aid in the development of biomarkers to assess the severity of pulmonary TB.  相似文献   
8.
The objective of this study was to evaluate the effects of partially replacing dry ground corn with glycerin on ruminal fermentation using a dual-flow continuous culture system. Six fermenters (1,223 ± 21 ml) were used in a replicated 3x3 Latin square arrangement with three periods of 10 d each, with 7 d for diet adaptation and 3 d for sample collections. All diets contained 75% concentrate and three dietary glycerin levels (0, 15, and 30% on dry matter basis), totaling six replicates per treatment. Fermenters were fed 72 g of dry matter/d equally divided in two meals/d, at 0800 and 2000 h. Solid and liquid dilution rates were adjusted daily to 5.5 and 11%/h, respectively. On d 8, 9, and 10, samples of 500 ml of solid and liquid digesta effluent were mixed, homogenized, and stored at -20°C. Subsamples of 10 ml were collected and preserved with 0.2 mL of a 50% H2SO4 solution for later determination of NH3-N and volatile fatty acids. Microbial biomass was isolated from fermenters for chemical analysis at the end of each experimental period. Data were analyzed using the MIXED procedure in SAS with α = 0.05. Glycerin levels did not affect apparent digestibility of DM (P Lin. = 0.13; P Quad. = 0.40), OM (P Lin. = 0.72; P Quad. = 0.15), NDF (P Lin. = 0.38; P Quad. = 0.50) and ADF (P Lin. = 0.91; P Quad. = 0.18). Also, glycerin inclusion did not affect true digestibility of DM (P Lin. = 0.35; P Quad. = 0.48), and OM (P Lin. = 0.08; P Quad. = 0.19). Concentrations of propionate (P < 0.01) and total volatile fatty acids (P < 0.01) increased linearly and concentrations of acetate (P < 0.01), butyrate (P = 0.01), iso-valerate (P < 0.01), and total branched-chain volatile fatty acids, as well as the acetate: propionate ratio (P < 0.01) decreased with glycerin inclusion. Linear increases on NH3-N concentration in digesta effluent (P < 0.01) and on NH3-N flow (P < 0.01) were observed due to glycerin inclusion in the diets. Crude protein digestibility (P = 0.04) and microbial N flow (P = 0.04) were greater in the control treatment compared with the other treatments and responded quadratically with glycerin inclusion. Furthermore, the inclusion of glycerin linearly decreased (P = 0.02) non-ammonia N flow. Glycerin levels did not affect the flows of total N (P Lin. = 0.79; P Quad. = 0.35), and dietary N (P Lin. = 0.99; P Quad. = 0.07), as well as microbial efficiency (P Lin. = 0.09; P Quad. = 0.07). These results suggest that partially replacing dry ground corn with glycerin may change ruminal fermentation, by increasing total volatile fatty acids, and propionate concentration without affecting microbial efficiency, which may improve glucogenic potential of beef cattle diets.  相似文献   
9.
Glycosyltransferases are normally synthesized as membrane-anchored proteins. However, we recently found that the murine enzyme UDP-Gal:Galβ1→4GLcNAc (Gal to Gal) a1,3 galactosyltransferase (a1,3GT) is secreted in a soluble form into media by mouse teratocarcinoma F9 cells (Cho SK, Yeh J-C, Cho M, Cummings RD (1996) J Biol Chem 271: 3238-46). To study the biosynthesis of this enzyme and whether secretion of the soluble enzyme is a general phenomenon, a solid-phase assay was developed for the a1,3GT activity. A recombinant and soluble form of the murine a1,3GT was produced in H293 cells (H293-a1,3GT) to aid in optimizing the assay. Desialylated orosomucoid was used as an immobilized acceptor in coated microtiter plates. The formation of product was detected by a biotinylated human-derived anti-a-Gal IgG and streptavidin conjugated to either alkaline phosphatase or the recombinant bioluminescent protein aequorin. Enzyme activity was dependent on the concentrations of asialoorosomucoid, UDP-Gal, a1,3GT and the time of incubation. The assay was also useful in monitoring a1,3GT activity during enzyme enrichment procedures. Using this assay, we found that a1,3GT activity was present in both cell extracts and culture media of several mammalian cell lines. Enzyme activity was also present in the sera from several mammals, but activity was absent in the sera from either humans or baboons. Our results demonstrate the development of a novel assay for the a1,3GT and provide evidence that secretion of the enzyme is a common biological phenomenon. This revised version was published online in November 2006 with corrections to the Cover Date.  相似文献   
10.

Background and Purpose

Liver cancer is the third leading cause of cancer mortality worldwide. The aim of this study was to investigate the frequency and characteristics of cerebral lipiodol embolism (CLE) in patients with hepatocellular carcinoma (HCC) receiving transarterial embolization/chemoembolization (TAE/TACE).

Methods

We reviewed all HCC patients who received TAE/TACE during the period of 2007 and 2013 at a university medical center. The frequency of CLE per procedure and the clinical manifestations of CLE, including the review of previous reported cases (n = 24), were analyzed.

Results

During the study period, a total of 7855 TAE/TACE procedures were conducted on 3277 patients. There were 8 patients (mean age 59±11 years; 5 males and 3 females) who developed CLE. The frequency of TAE/TACE-related CLE was 1.02 (95% CI, 0.44–2.01) per 1000 procedures. Acute disturbance of consciousness and respiratory distress after TAE/TACE were the most common presentations of CLE. All patients had disseminated infarcts involving both the anterior and posterior cerebral circulations. For 3 patients with shunting between the tumor feeding artery and the pulmonary vein, a specific imaging pattern of coexisting scattered hyperdense spots was found. Furthermore, combined with our 8 cases, the total of 32 cases indicated that old age and female sex were the two risk factors for poor outcome after CLE.

Conclusions

CLE is a rare but potentially serious complication in HCC patients receiving TAE/TACE. The clinical characteristics of CLE summarized in our study would help facilitate the ability of clinicians to provide timely diagnosis and management.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号