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951.
目的 研究人氨酰基脯氨酸二肽酶除催化水解C端为脯氨酸残基的二肽外 ,是否还有G类有机磷化合物水解酶 (G酶)活性。方法 用基因工程技术克隆及表达人的重组氨酰基脯氨酸二肽酶。氨酰基脯氨酸二肽酶及G酶活性用常规方法测定。结果 COS 7细胞表达的人氨酰基脯氨酸二肽酶催化有机磷化合物梭曼的水解 ,也水解二肽化合物Gly Pro。两种活性比未转染的COS 7细胞高 2倍。比较转染了带有氨酰基脯氨酸二肽酶基因的重组载体的COS 7细胞和对照组细胞中的两种酶活性 ,可以看到有平行的升高趋势及恒定的酶活性比值。结论G酶和氨酰基脯氨酸二肽酶为同一个酶 ,或至少属于同工酶 相似文献
952.
S. Vichier‐Guerre R. Lo‐Man L. BenMohamed E. Driaud S. Kovats C. Leclerc S. Bay 《Chemical biology & drug design》2003,62(3):117-124
Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor‐associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte‐associated antigens (HLA). In order to stimulate a T‐cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B‐cell epitope (Tn antigen: α‐GalNAc‐Ser) covalently linked to peptides corresponding to the Pan DR ‘universal’ T‐helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA‐DR1, and HLA‐DR4). A strong T‐cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use. 相似文献
953.
Adamopoulos DA 《International journal of andrology》2000,23(6):320-331
The effectiveness of medical treatment for idiopathic oligozoospermia (IO) has been at best doubtful until now and a logical consequence of this unsatisfactory situation has been the partial displacement of this approach by assisted reproduction techniques. This state of affairs has resulted from insufficient investigation, inappropriately designed clinical trials and consistent disregard for the principles of evidence-based medicine. Protocol-related shortcomings and wrong interpretation of the data available have also been some of the all too frequent problems encountered in this therapeutic approach. In this rather misty situation, it appears that, of the therapeutic agents used so far, follicle stimulating hormone (FSH) (mainly FSH-secretagogues) may exert some beneficial effects on a number of biological endpoints related to spermatogenesis and sperm maturation. The short and medium term prospects of medical treatment for IO rest mainly with improvement of investigative procedures to a higher degree of sophistication, with emphasis placed on identifying the causes rather than the results of dysfunction so that a better selection of candidates can be made. Moreover, the introduction of prognostic indices for evaluation of the beneficial effects of a therapeutic agent may be of paramount importance. Finally, a better assessment of the preparations available and, possibly, the introduction of new more specific agents may also be an important step forward in this field. This type of large-scale effort should not be left to individual investigators or special centres working independently, but it may come under the auspices of a central regulating agency so that undisputed results from large, multicentre and uniform studies might be obtained, if medical treatment is to remain a good option. In this context, it may also be emphasized that andrology's main task should always be to treat the male with the problem rather than his healthy female partner, whenever this is possible. 相似文献
954.
955.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(10):679-682
The promising β‐amyloid PET imaging agent, [11C]‐6‐OH‐BTA‐1, has been radiolabelled in one step using [11C]‐methyl triflate. No protection of the 6‐hydroxy group is required, greatly simplifying the synthetic method. The reaction may be carried out in solution or by the captive solvent ‘loop’ method. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
956.
Thomas A. Krenitsky John Dillberger Elena Zotova Joseph C. Arezzo James B. Koprich Farzad Mortazavi Timothy A. Gates Gary L. Dunbar 《Drug development research》2004,62(1):60-70
In cultured cells, KP544 [2‐amino‐5‐(4‐chlorophenylethynyl)‐4‐(4‐trans‐hydroxycyclohexyl amino) pyrimidine] amplifies differentiation initiated by nerve growth factor (NGF) or cAMP. This report describes the pharmacokinetics, safety, and neuroprotective efficacy of KP544 in rats. After an oral dose of 10 mg/kg KP544 was 25% bioavailable with a plasma half‐life of 1.3 h and brain levels 6‐fold higher than plasma levels at 4 and 8 h post‐dose. In a safety study, daily oral dosing for 30 days at 10 and 100 mg/kg was well tolerated. The favorable pharmacokinetic and safety profiles, together with its amplification of NGF in vitro, prompted evaluation of KP544 in two models involving NGF deficiencies. In the first model, brains were lesioned with intrastriatal injections of quinolinic acid. KP544 at oral doses of 0.02 to 1.0 mg/kg/day almost completely prevented the resulting learning deficits as evaluated using a radial‐arm‐water maze. At the lowest dose, there was a slower onset of functional improvement. These effects were accompanied by reductions (16–34%) in the striatal lesion size that were greatest at the highest dose and comparable to those seen with NGF therapy. The second model involved a peripheral neuropathy induced by taxol that is associated with decreases in NGF. KP544 at oral doses of 0.1–10 mg/kg/day decreased the severity of the neuropathy as measured by caudal nerve conduction velocities (30–70% return to control values). In both models, KP544 had a large therapeutic index suggesting its potential as a new approach for treating clinical disorders involving deficiencies in NGF. Drug Dev. Res. 62:60–70, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
957.
M. Cruz J.M. Tusell D. Grillo‐Bosch F. Albericio J. Serratosa F. Rabanal E. Giralt 《Chemical biology & drug design》2004,63(3):324-328
Abstract: Single N‐methyl amino acid‐containing peptides related to the central hydrophobic region β16–20 (Lys‐Leu‐Val‐Phe‐Phe) of the β‐amyloid protein are able to reduce the cytotoxicity of natural β1–42 in PC12 cell cultures. N‐methyl phenylalanine analogs yield statistically significant increments in cell viability (Student's t‐test < 0.01%) and are nontoxic in the same assay. These promising results indicate that these peptide molecules could be a starting point for the development of potential therapeutic compounds for the treatment of Alzheimer's disease. 相似文献
958.
959.
人乳头瘤病毒感染与宫颈癌前病变和宫颈癌及其预后的关系 总被引:2,自引:0,他引:2
目的 :探讨人乳头瘤病毒 (humanpapillomavirus ,HPV)与宫颈癌前病变 (cervi calintraepithelialneoplasia ,CIN)和宫颈癌的关系以及与它们的预后关系。方法 :采用第 2代杂交捕获试验法检测我院门诊和住院患者 994例随访手术治疗患者 99例 ,随访患者同时行宫颈细胞学、阴道镜检查 ,以病理结果为金标准 ,按宫颈病变严重程度比较高危型HPV的检出率 ,以及比较术前术后宫颈癌前病变、宫颈癌感染高危型HPV变化情况。结果 :以HPVDNA≥ 1 0pg/mL为阳性标准 ,慢性宫颈炎、CIN各组及宫颈癌分别为 46 92 % ( 2 0 6/4 3 9)、65 71% ( 2 3 /3 5 )、81 82 % ( 3 6/4 4)、 98 41%( 62 /63 )、82 3 2 % ( 3 40 /4 13 )。随访患者细胞学 ,阴道镜检查除 1例CIN3患者为阳性 ,其余均为阴性 ,术后HPV持续阳性率为 2 1 18% ,其中 1例诊断为宫颈原位癌。结论 :高危型HPV感染与宫颈癌前病变和宫颈癌有明显相关性 ;宫颈锥切术后HPV持续阳性患者为复发的高危人群 ,应严密随访 相似文献
960.
"彗星"分析法检测人癌裸鼠移植瘤的放射敏感性 总被引:3,自引:0,他引:3
目的 探讨“彗星”分析法应用于人实体肿瘤放射敏感性检测的可能性。方法 应用“彗星”分析法 ,以尾力距之比 (RTM)作为终指标 ,检测人肺腺癌、人食管鳞癌和人鼻咽鳞癌等 3种人癌裸小鼠移植瘤的放射敏感性。裸小鼠移植瘤组织被消化并稀释成细胞浓度为 4× 10 4ml的单细胞悬液后 ,分成对照组 (0Gy)和不同剂量照射组 ,照射组分别给予 2、5、10和 15Gy的 6MVX射线的冰上照射 ,照射后立即进行“彗星”分析。结果 3种人癌裸小鼠移植瘤细胞未照射时 (0Gy)的尾力矩 (TM)差异有显著性意义 (F =9.11,P <0 .0 1)。不同剂量 (2、5、10和 15Gy)照射后 ,3种人癌裸小鼠移植瘤细胞未做校正时的TM所反映放射敏感性由高到低的变化趋势依次为 :肺腺癌 >食管鳞癌 >鼻咽鳞癌 ,显然与临床一般印象不符 ;而经与对照组进行“本底”校正后的RTM所反映放射敏感性由高到低的变化趋势依次为 :食管鳞癌 >鼻咽鳞癌 >肺腺癌 ,则符合临床一般印象。结论 ①应用“彗星”分析法检测实体肿瘤的放射敏感性 ,尾力矩必须进行“本底”校正 ,即扣除对照组本底误差后的尾力矩才能很好地反映实体肿瘤的放射敏感性差异。②“彗星”分析法可用于检测人体肿瘤组织的放射敏感性。 相似文献