全文获取类型
收费全文 | 10446篇 |
免费 | 711篇 |
国内免费 | 59篇 |
专业分类
耳鼻咽喉 | 208篇 |
儿科学 | 306篇 |
妇产科学 | 310篇 |
基础医学 | 1273篇 |
口腔科学 | 189篇 |
临床医学 | 1223篇 |
内科学 | 2468篇 |
皮肤病学 | 95篇 |
神经病学 | 874篇 |
特种医学 | 554篇 |
外科学 | 1184篇 |
综合类 | 151篇 |
一般理论 | 8篇 |
预防医学 | 725篇 |
眼科学 | 174篇 |
药学 | 774篇 |
中国医学 | 6篇 |
肿瘤学 | 694篇 |
出版年
2021年 | 100篇 |
2020年 | 63篇 |
2019年 | 95篇 |
2018年 | 146篇 |
2017年 | 114篇 |
2016年 | 119篇 |
2015年 | 143篇 |
2014年 | 221篇 |
2013年 | 279篇 |
2012年 | 414篇 |
2011年 | 447篇 |
2010年 | 260篇 |
2009年 | 212篇 |
2008年 | 382篇 |
2007年 | 435篇 |
2006年 | 410篇 |
2005年 | 397篇 |
2004年 | 455篇 |
2003年 | 390篇 |
2002年 | 390篇 |
2001年 | 378篇 |
2000年 | 343篇 |
1999年 | 325篇 |
1998年 | 166篇 |
1997年 | 143篇 |
1996年 | 173篇 |
1995年 | 150篇 |
1994年 | 135篇 |
1993年 | 116篇 |
1992年 | 345篇 |
1991年 | 319篇 |
1990年 | 271篇 |
1989年 | 309篇 |
1988年 | 228篇 |
1987年 | 242篇 |
1986年 | 221篇 |
1985年 | 194篇 |
1984年 | 151篇 |
1983年 | 134篇 |
1982年 | 106篇 |
1981年 | 73篇 |
1980年 | 93篇 |
1979年 | 138篇 |
1978年 | 99篇 |
1977年 | 67篇 |
1975年 | 83篇 |
1974年 | 94篇 |
1973年 | 70篇 |
1972年 | 72篇 |
1971年 | 64篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
P D Williams M G Bock R D Tung V M Garsky D S Perlow J M Erb G F Lundell N P Gould W L Whitter J B Hoffman 《Journal of medicinal chemistry》1992,35(21):3905-3918
A new structural class of cyclic hexapeptide oxytocin antagonists derived from Streptomyces silvensis and typified by L-365,209 (cyclo-[L-prolyl1-D-phenylalanyl2-L- isoleucyl3-D-dehydropiperazyl4-L-dehydroperazyl5-D-(N- methyl)phenylalanyl6]) was recently reported. In this paper we further delineate the structure-activity profile for this new class by systematic study of L-365,209 analogs obtained by total synthesis. The optimal combination of cyclic amino acid ring sizes at positions 1, 4, and 5 and the role of the N-alkyl substituent at position 6 was elucidated. The lipophilic amino acids at positions 2 and 3 and the unusual amino acid D-dehydropiperazic acid at position 4 were found to be the most critical residues for obtaining good oxytocin receptor affinity. Analogs containing a basic side chain at the less critical 5- and 6-positions maintained good receptor affinity and also had useful levels of water solubility for intravenous formulation. By combining potency- and solubility-enhancing substitutions, several analogs were identified that have the desired combination of properties in vitro (22, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L-pipeco lyl-D- histidyl]; 25, cyclo-[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L -pipecolyl-D- histidyl]; 26, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-dehydropiperazyl-L-++ pipecolyl-D-histidyl]; 33, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L- piperazinylcarboxy-D-(N-methyl)phenylalanyl]; 34, cyclo-[L-prolyl-D-phenylalanyl-L-isoleucyl-D-dehydropiperazyl-L-or nithyl- D-(N-methyl)phenylalanyl]). In general, this class exhibited good selectivity for binding to the oxytocin receptor versus the arginine vasopressin V1a and V2 receptor subtypes, although increased V2 receptor affinity was observed in one case (32, cyclo[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L- lysyl-D-(N- methyl)phenylalanyl]). Unexpectedly, compound 33 was found to stimulate contractions of the isolated rat uterus via activation of the uterine bradykinin receptor. Compounds 22, 25, 26, 33, and 34 were found to be potent antagonists of oxytocin-stimulated contraction of the rat uterus in vitro and in vivo. Compounds 22 and 25 were additionally characterized as potent antagonists of oxytocin-stimulated uterine contractions in the near-term pregnant rhesus monkey. These studies thus demonstrate the selectivity and efficacy of certain members of this novel class of antagonists and suggest their use as pharmacological tools in further defining the role of oxytocin in both term and preterm labor. 相似文献
72.
Total lower abdominal wall resection was required to remove a recurrent exophytic bladder carcinoma in a 36-year-old woman. The resulting 25 x 30-cm fascial defect was repaired with Marlex mesh. Bilateral rectus femoris myocutaneous flaps were rotated to close the 25 x 18-cm area of skin deficiency. These provided the advantages of robust cover of the lower abdominal wall in a single-stage procedure and primary closure of the donor sites. 相似文献
73.
P G Prokocimer M Maze B B Hoffman 《The Journal of pharmacology and experimental therapeutics》1987,241(3):870-874
Hypertension due to pheochromocytoma is generally considered to be a straightforward, direct consequence of the elevated concentrations of circulating catecholamines. However, clonidine, a centrally acting antihypertensive drug, has been reported to lower blood pressure in patients with pheochromocytoma, suggesting the possibility that the sympathetic nervous system is involved in the maintenance of hypertension in this disease. We have investigated this possibility in New England Deaconess Hospital rats harboring a transplantable pheochromocytoma that secretes norepinephrine and dopamine. Both clonidine and chlorisondamine, a ganglionic blocker, markedly decreased blood pressure in tumor-bearing rats. However, in other rats made acutely hypertensive with a norepinephrine infusion, neither clonidine nor chlorisondamine decreased blood pressure. This result indicates that in an acute model of hypertension, where baroreflex mechanisms have likely withdrawn sympathetic tone, neither clonidine nor chlorisondamine had nonspecific antihypertensive effects. A central nervous system site of action for the antihypertensive effect of clonidine in the rats harboring pheochromocytoma was suggested by the observation that the opiate antagonist naloxone both reversed and prevented clonidine's effect on blood pressure. Prazosin and yohimbine were utilized to determine the respective contributions of alpha-1 and alpha-2 adrenergic receptors in the maintenance of hypertension in rats harboring pheochromocytoma. Both drugs markedly lowered blood pressure in these rats. Our data suggest that both the sympathetic nervous system and circulating catecholamines are involved in the maintenance of hypertension due to pheochromocytoma. 相似文献
74.
D K Robie R H Pearl C Gonsales R D Restuccia M A Hoffman 《Journal of pediatric surgery》1991,26(8):971-3; discussion 973-4
A case is reported of recurrent laryngotracheoesophageal cleft following two attempted repairs. The anterior approach to the larynx and trachea provided excellent exposure for defining the extent of the recurrent cleft, and allowed precise anatomic repair. Neurovascular structures were easily avoided by this operative method. Of 170 clefts reported in the literature, 19 recurred necessitating reoperation. The anterior approach to the larynx and trachea is appropriate in recurrent clefts and may be preferable at the initial repair. 相似文献
75.
O W Woltersdorf H Schwam J B Bicking S L Brown S J deSolms D R Fishman S L Graham P D Gautheron J M Hoffman R D Larson 《Journal of medicinal chemistry》1989,32(11):2486-2492
A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined. In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation. The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4. Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor. 相似文献
76.
77.
Quantitation of complex brain function in children: preliminary evaluation using a nonhuman primate behavioral test battery 总被引:2,自引:0,他引:2
The performance of twenty children (3-11 years of age) in a complex operant test battery (OTB) was evaluated. The operant schedules, or tasks, used in the OTB were identical to those originally designed and currently used to assess complex brain function in nonhuman primate laboratory animals (monkeys). The OTB consisted of five operant tasks: 1) Progressive-Ratio [PR]; 2) Conditioned-Position Responding [CPR]; 3) Temporal Response Differentiation [TRD]; 4) Delayed Matching-to-Sample [DMTS] and 5) Incremental Repeated Acquisition [IRA]. These operant tasks are thought to engender responding indicative of processes associated with: 1) motivation; 2) color and position discrimination; 3) time-perception; 4) short-term memory and attention; and 5) learning, respectively. The parameters for each of the tasks in the OTB were optimized for use in the clinical setting to assess cognitive function in children. In the small population studied, performance in the IRA, DMB and TRD tasks was age related. Of the four 6-yr-olds studied, only those categorized as having either learning disabilities (LD, n = 1) or attention deficit disorders (ADD, n = 2) did not complete the "learning" task. By comparison of human and monkey performance in the OTB, we also hope to validate the use of laboratory animal models in research efforts designed to yield insight into complex human brain function. It is also hoped that assessment of children's performance in the tasks in the OTB will assist in the diagnosis and treatment of certain childhood disorders such as learning disabilities and/or attention deficit disorders. 相似文献
78.
Immobilization and characterization of beta-galactosidase in thermally reversible hydrogel beads 总被引:1,自引:0,他引:1
Beta-Galactosidase has been immobilized within thermally reversible hydrogel beads and has been studied in batch and packed bed reactor systems. The enzyme was entrapped in a copolymer hydrogel of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) as beads were formed in an inverse suspension polymerization. A reversible deswelling and reswelling of the hydrogel matrix was induced by first warming and then cooling through 37-40 degrees C, which is the lower critical solution temperature, LCST, of the backbone copolymer. The optimum temperature for maximum activity of the immobilized enzyme-gel bead system was found to be 30-35 degrees C in a batch mode and 40 degrees C in a packed bed reactor, which were both below the 50 degrees C optimum for the free enzyme. These differences are understandable, since the mass transfer rates of substrate and product within the pores of the gel matrix are controlled mainly by the temperature, so therefore it is the temperature which governs the overall activity of the immobilized enzyme system. It was also found that when the operational temperature in the packed bed reactor was cycled between temperatures below (35 degrees C) and above (45 degrees C) the copolymer gel LCST, the activity of the immobilized enzyme almost fully recovered after each cycle. In fact, the enzyme-gel system exhibited a complete "shut-off" in activity at 50 degrees C which was the temperature where the free enzyme showed its maximum activity. The thermal cycling operation of LCST enzyme-gel beads can be used to enhance overall activity and productivity of a packed bed reactor, when compared to isothermal operation of this reactor. This is due to the thermally induced "pumping" which enhances mass transfer rates of substrate in and product out of the gel beads. 相似文献
79.
Hoffman AS 《Clinical materials》1992,11(1-4):13-18
An important trend in biomaterials research and development is the synthesis of polymers, which combine capabilities of biologic recognition ('biomimetic') with special physicochemical properties of the synthetic polymer system. For example, an antibody may be conjugated to the backbone of a polymer which precipitates upon small changes in pH, temperature, or ionic strength. Crosslinked gels may also be synthesized from such polymers, and a biomolecule such as an enzyme may be chemically or physically entrapped in these gels. Such gels will shrink and swell in response to small changes in environmental stimuli. Another approach is to 'engineer', perhaps via computer-aided molecular design, new artificial biomimetic systems by exact placement of functional groups on rigid polymer backbones, crosslinked structures, or macromolecular assemblies. In this way, biocatalytic functioning or biorecognition similar to enzymes and antibodies can be achieved without the inherent instability often encountered with the native biomolecules or assemblies. In addition to these synthetic approaches, new and exciting analytical tools, such as the scanning tunnelling microscope and the atomic force microscope, are permitting visualization of individual and small clusters of proteins and other biomolecules on surfaces. Cell attachments and spreading may also be visualized at various depths within the cell using the confocal laser microscope. Such analytical techniques can lead to important new knowledge about biologic interactions with biomaterials, and, therefore, to development of even more biocompatible implants and devices. This paper overviews the field of polymeric biomaterials and highlights the important emerging trends in synthesis and analysis of these materials. 相似文献
80.
Pollution prevention as a market-enhancing strategy: a storehouse of economical and environmental opportunities
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hoffman JS 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(3):832-834
EPA's (Environmental Protection Agency) Green Lights Program for energy-efficient lighting illustrates the economic benefits and the market-transforming value of a pollution prevention philosophy. Using technologies available today, and assuming current prices, this program is expected to reduce air pollution 5%, while saving the nation's businesses up to 20 billion in electric bills every year. However, these pollution prevention and savings estimates may be low. As Green Lights transforms the market for lighting services by creating a higher demand for better technologies at lower costs, the program will likely achieve even larger pollution reductions and electricity savings. 相似文献