全文获取类型
收费全文 | 11440篇 |
免费 | 708篇 |
国内免费 | 43篇 |
专业分类
耳鼻咽喉 | 79篇 |
儿科学 | 253篇 |
妇产科学 | 200篇 |
基础医学 | 1535篇 |
口腔科学 | 317篇 |
临床医学 | 893篇 |
内科学 | 2695篇 |
皮肤病学 | 213篇 |
神经病学 | 884篇 |
特种医学 | 1063篇 |
外科学 | 1905篇 |
综合类 | 73篇 |
一般理论 | 2篇 |
预防医学 | 596篇 |
眼科学 | 175篇 |
药学 | 575篇 |
1篇 | |
中国医学 | 9篇 |
肿瘤学 | 723篇 |
出版年
2023年 | 117篇 |
2022年 | 235篇 |
2021年 | 391篇 |
2020年 | 250篇 |
2019年 | 304篇 |
2018年 | 361篇 |
2017年 | 230篇 |
2016年 | 311篇 |
2015年 | 356篇 |
2014年 | 433篇 |
2013年 | 464篇 |
2012年 | 735篇 |
2011年 | 688篇 |
2010年 | 472篇 |
2009年 | 382篇 |
2008年 | 578篇 |
2007年 | 602篇 |
2006年 | 602篇 |
2005年 | 585篇 |
2004年 | 480篇 |
2003年 | 416篇 |
2002年 | 401篇 |
2001年 | 156篇 |
2000年 | 141篇 |
1999年 | 141篇 |
1998年 | 100篇 |
1997年 | 108篇 |
1996年 | 74篇 |
1995年 | 61篇 |
1994年 | 69篇 |
1993年 | 53篇 |
1992年 | 67篇 |
1991年 | 73篇 |
1990年 | 80篇 |
1989年 | 62篇 |
1988年 | 62篇 |
1987年 | 76篇 |
1986年 | 53篇 |
1985年 | 66篇 |
1984年 | 52篇 |
1983年 | 39篇 |
1982年 | 38篇 |
1981年 | 43篇 |
1979年 | 41篇 |
1978年 | 36篇 |
1977年 | 38篇 |
1976年 | 36篇 |
1974年 | 38篇 |
1971年 | 33篇 |
1932年 | 36篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
The purpose of this study was to examine absorption of basic drugs as a function of the composite solubility curve and intestinally relevant pH by using a gastrointestinal tract (GIT) absorption simulation based on the advanced compartmental absorption and transit model. Absorption simulations were carried out for virtual monobasic drugs having a range of pKa, log D, and dose values as a function of presumed solubility and permeability. Results were normally expressed as the combination that resulted in 25% absorption. Absorption of basic drugs was found to be a function of the whole solubility/pH relationship rather than a single solubility value at pH 7. In addition, the parameter spaces of greatest sensitivity were identified. We compared 3 theoretical scenarios: the GIT pH range overlapping (1) only the salt solubility curve, (2) the salt and base solubility curves, or (3) only the base curve. Experimental solubilities of 32 compounds were determined at pHs of 2.2 and 7.4, and they nearly all fitted into 2 of the postulated scenarios. Typically, base solubilities can be simulated in silico, but salt solubilities at low pH can only be measured. We concluded that quality absorption simulations of candidate drugs in most cases require experimental solubility determination at 2 pHs, to permit calculation of the whole solubility/pH profile. 相似文献
102.
Grases F Costa-Bauzá A Königsberger E Königsberger LC 《International urology and nephrology》2000,32(1):19-27
Calcium renal lithiasis formation depends on the balance between thermodynamic (supersaturation) and kinetic (inhibitors,
nucleants)factors. In this paper, the importance of both groups was evaluated using(a) the complete urine analysis data obtained
from 32 healthy volunteers and 141 active stone-formers, and (b) a comprehensive computer model to calculate the supersaturation
values of calcium oxalate monohydrate,hydroxyapatite and brushite in each urine sample. The results of this evaluation were
used to assess the possible effectiveness of a given pharmacological treatment.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
103.
Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1. 总被引:2,自引:0,他引:2
George A Mashour Pablo Hernáiz Driever Melanie Hartmann Stephanie N Drissel Tingguo Zhang Bianca Scharf Ursula Felderhoff-Müser Sadatoshi Sakuma Reinhard E Friedrich Robert L Martuza Victor Felix Mautner Andreas Kurtz 《Clinical cancer research》2004,10(17):5677-5683
PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis. 相似文献
104.
105.
The relationship of serum-eosinophil cationic protein and eosinophil count to disease activity in children with bronchial asthma 总被引:1,自引:0,他引:1
106.
107.
Marie A McAnuff Wayne W Harding Felix O Omoruyi Helen Jacobs Errol Y Morrison Helen N Asemota 《Food and chemical toxicology》2005,43(11):1667-1672
In this study, three steroidal sapogenins (Delta3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and beta-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of alpha-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+-K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+-K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight. 相似文献
108.
Hans-Peter Gschwind Ulrike Pfaar Felix Waldmeier Markus Zollinger Claudia Sayer Peter Zbinden Michael Hayes Rolf Pokorny Michael Seiberling Monique Ben-Am Bin Peng Gerhard Gross 《Drug metabolism and disposition》2005,33(10):1503-1512
Imatinib mesylate (GLEEVEC, GLIVEC, formerly STI571) has demonstrated unprecedented efficacy as first-line therapy for treatment for all phases of chronic myelogenous leukemia and metastatic and unresectable malignant gastrointestinal stromal tumors. Disposition and biotransformation of imatinib were studied in four male healthy volunteers after a single oral dose of 239 mg of (14)C-labeled imatinib mesylate. Biological fluids were analyzed for total radioactivity, imatinib, and its main metabolite CGP74588. Metabolite patterns were determined by radio-high-performance liquid chromatography with off-line microplate solid scintillation counting and characterized by liquid chromatography-mass spectrometry. Imatinib treatment was well tolerated without serious adverse events. Absorption was rapid (t(max) 1-2 h) and complete with imatinib as the major radioactive compound in plasma. Maximum plasma concentrations were 0.921 +/- 0.095 mug/ml (mean +/- S.D., n = 4) for imatinib and 0.115 +/- 0.026 mug/ml for the pharmacologically active N-desmethyl metabolite (CGP74588). Mean plasma terminal elimination half-lives were 13.5 +/- 0.9 h for imatinib, 20.6 +/- 1.7 h for CGP74588, and 57.3 +/- 12.5 h for (14)C radioactivity. Imatinib was predominantly cleared through oxidative metabolism. Approximately 65 and 9% of total systemic exposure [AUC(0-24 h) (area under the concentration time curve) of radioactivity] corresponded to imatinib and CGP74588, respectively. The remaining proportion corresponded mainly to oxidized derivatives of imatinib and CGP74588. Imatinib and its metabolites were excreted predominantly via the biliary-fecal route. Excretion of radioactivity was slow with a mean radiocarbon recovery of 80% within 7 days (67% in feces, 13% in urine). Approximately 28 and 13% of the dose in the excreta corresponded to imatinib and CGP74588, respectively. 相似文献
109.
PURPOSE: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single-dose pharmacokinetics of lamotrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers. METHODS: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this single-dose, two-period, crossover study with a 2-week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation. RESULTS: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 +/- 9.5 microg/mL/hr after rectal administration and 51.71 +/- 19.2 microg/mL/hr after oral administration. The average maximum LTG concentration was 0.53 +/- 0.14 microg/mL after rectal administration and 1.45 +/- 0.35 microg/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 +/- 0.33 for rectal administration. There were no drug-related rashes or serious side effects. CONCLUSIONS: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally. 相似文献
110.
The endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline (salsolinol), which is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been reported to inhibit mitochondrial complex I (NADH-Q reductase) activity as does the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP(+)). However, the mechanism of salsolinol leading to neuronal cell death is still unknown. Thus, we correlated indices of cellular energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to salsolinol and compared these results with data obtained with MPP(+). Both toxins induce time and dose-dependent decrease in cell survival with IC(50) values of 34 microM and 94 microM after 72 h for salsolinol and MPP(+), respectively. Furthermore, salsolinol and MPP(+) produce a decrease of intracellular net ATP content with IC(50) values of 62 microM and 66 microM after 48 h, respectively. In contrast to MPP(+), salsolinol does not induce an increase of intracellular net NADH content. In addition, enhancing glycolysis by adding D-glucose to the culture medium protects the cells against MPP(+) but not salsolinol induced cellular ATP depletion and cytotoxicity. These results suggest that cell death induced by salsolinol is due to impairment of cellular energy supply, caused in particular by inhibition of mitochondrial complex II (succinate-Q reductase), but not complex I. 相似文献