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131.
BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1muM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site.  相似文献   
132.
AIMS: To compare long-term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes. METHODS: This was a double-blind, multicentre, comparative, parallel group trial in 283 patients with Type 2 diabetes, who were randomized to receive 1-year treatment with pioglitazone 30-45 mg/day or gliclazide 80-320 mg/day. Drug dose was titrated on the basis of self-monitored blood glucose (SMBG) measurements and HbA1c values. The 1-year changes in HbA1c, fasting blood glucose (FBG), insulin, HOMA-S (HOmeostatic Model Assessment) and SMBG were compared. In a subgroup of patients (n = 10), systemic glucose production and utilization were determined by a combination of isotopic (deuterated glucose) and clamp techniques. RESULTS: In both groups, there were similar decreases in HbA1c (pioglitazone: -0.79%; gliclazide: -0.79%) and FBG (pioglitazone: -1.0 mmol/l; gliclazide: -0.7 mmol/l), whereas the slope of the reduction of fasting blood glucose was different between groups (P = 0.004). Insulin levels as well as insulin resistance assessed using HOMA-S decreased significantly only after pioglitazone treatment (-11.94 pmol/l and -1.03, respectively, both P = 0.002 vs. baseline). A significantly greater reduction in systemic glucose production was observed in the pioglitazone group (-2.48 micromol/kg/min, P = 0.042) than in the gliclazide group (-1.02 micromol/kg/min). A few, mild adverse events occurred in both groups. CONCLUSIONS: A comparable decrease in HbA1c and FBG was observed with pioglitazone and gliclazide. However, with pioglitazone there was a continuous decrease in FBG over 1 year, whereas gliclazide failed to maintain a similar trend. This favourable effect of pioglitazone was due to its insulin-sensitizing effect and ability to decrease systemic glucose production.  相似文献   
133.
茶色素对冠心病及高血压病病人血小板功能的影响   总被引:1,自引:0,他引:1  
目的:探索茶色素对冠心病、高血压病病人血小板功能的影响。方法:冠心病病人36例(男性21例,女性15例;年龄64±s4a);高血压病病人30例(男性18例,女性12例;年龄58±8a)。采用茶色素250mg,po,tid,30d为一个疗程。结果:治疗后TXB2下降,6-keto-PGP1α上升,TXB2/6-keto-PGF1α比值下降(P<0.01或P<0.05),GMP-140下降(P<0.05),PagT,PadT下降(P<0.05)。结论:茶色素具有降低血小板表面活性作用,抑制血小板聚集和粘附,抗血栓形成,改善微循环,对冠心病和高血压病病人起到积极的防治作用。  相似文献   
134.
135.
Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and td of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and td between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t1/2 (7.12 h), while apparent t1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for Cmax and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.  相似文献   
136.
Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.  相似文献   
137.
肝动脉化疗栓塞术治疗肝癌的临床与病理的联系   总被引:1,自引:0,他引:1  
梁力建  林汉良 《癌症》1993,12(2):148-150
作者将9例肝动脉化疗栓塞术(HAE)后二期切除的肝癌标本,多处切片作病理检查,结合病人的临床过程分析HAE的治疗作用,肝癌包膜对HAE的影响,HAE的效果及HAE后手术的时机等。作者认为,HAE对肝癌的治疗效果是姑息性的,故HAE后应争取在30~60天内再手三术探查,争取切除肿瘤。否则,HAE后肝癌复发的可能性极大。  相似文献   
138.
This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.  相似文献   
139.
A case series of 5 male patients afflicted with breast carcinoma is reported. The Authors describe symptomatology, diagnostic iter, principles of surgical treatment and results. Underlined is the wider surgical demolition in male breast cancer in comparison with females, even if natural history and biological conduct are comparable. This is because in male breast carcinoma the local and remote infiltration is more rapid than female for the less development of breast gland. Finally, indications for radiochemotherapy are comparable to female breast cancer.  相似文献   
140.
大鼠肝细胞Ⅰ,Ⅲ型前胶原基因表达及PDGF的影响   总被引:3,自引:1,他引:2  
目的观察大鼠肝细胞Ⅰ,Ⅲ型前胶原基因的表达及PDGF对其表达的影响.方法应用原位杂交技术检测分离培养的SD大鼠肝细胞(n=30)内Ⅰ,Ⅲ型前胶原基因的表达.同时观察10μg/L(n=30)和30μg/L(n=30)PDGF促进前胶原基因表达的作用.测定基因表达颗粒总面积占细胞总面积的百分比,并作比较分析.结果无论正常肝细胞或是在两种浓度的PDGF存在时,肝细胞内均可见到Ⅰ,Ⅲ型前胶原基因的表达.正常肝细胞Ⅰ,Ⅲ型前胶原基因表达面积的百分比(%)为77±19和75±21;加10μg/LPDGF后为115±19和112±10,而加30μg/L后为152±34及181±28,且在后者中表达明显增强(P<005及P<001).结论PDGF在转录水平上促进肝细胞胶原的合成.  相似文献   
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