全文获取类型
收费全文 | 11586篇 |
免费 | 1028篇 |
国内免费 | 25篇 |
专业分类
耳鼻咽喉 | 160篇 |
儿科学 | 318篇 |
妇产科学 | 428篇 |
基础医学 | 1817篇 |
口腔科学 | 265篇 |
临床医学 | 1263篇 |
内科学 | 2264篇 |
皮肤病学 | 272篇 |
神经病学 | 1075篇 |
特种医学 | 388篇 |
外科学 | 1322篇 |
综合类 | 249篇 |
一般理论 | 5篇 |
预防医学 | 953篇 |
眼科学 | 168篇 |
药学 | 841篇 |
中国医学 | 37篇 |
肿瘤学 | 814篇 |
出版年
2023年 | 81篇 |
2022年 | 174篇 |
2021年 | 344篇 |
2020年 | 170篇 |
2019年 | 270篇 |
2018年 | 313篇 |
2017年 | 232篇 |
2016年 | 270篇 |
2015年 | 272篇 |
2014年 | 373篇 |
2013年 | 510篇 |
2012年 | 671篇 |
2011年 | 775篇 |
2010年 | 466篇 |
2009年 | 397篇 |
2008年 | 634篇 |
2007年 | 617篇 |
2006年 | 574篇 |
2005年 | 574篇 |
2004年 | 525篇 |
2003年 | 452篇 |
2002年 | 404篇 |
2001年 | 220篇 |
2000年 | 218篇 |
1999年 | 185篇 |
1998年 | 109篇 |
1997年 | 82篇 |
1996年 | 89篇 |
1995年 | 80篇 |
1994年 | 83篇 |
1993年 | 71篇 |
1992年 | 131篇 |
1991年 | 140篇 |
1990年 | 142篇 |
1989年 | 143篇 |
1988年 | 136篇 |
1987年 | 144篇 |
1986年 | 127篇 |
1985年 | 121篇 |
1984年 | 109篇 |
1983年 | 88篇 |
1982年 | 72篇 |
1979年 | 78篇 |
1978年 | 65篇 |
1975年 | 50篇 |
1974年 | 69篇 |
1973年 | 72篇 |
1972年 | 55篇 |
1971年 | 53篇 |
1969年 | 56篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Evolutionary genetic analysis of the emergence of epidemic Vibrio cholerae isolates on the basis of comparative nucleotide sequence analysis and multilocus virulence gene profiles 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Vibrio cholerae, the causative agent of cholera, is a natural inhabitant of the aquatic ecosystem. We examined a unique collection of V. cholerae clinical and environmental isolates of widespread geographic distribution recovered over a 60-year period to determine their evolutionary genetic relationships based on analysis of two housekeeping genes, malate dehydrogenase (mdh) and a chaperonin (groEL). In addition, the phylogenetic distribution of 12 regions associated with virulence was determined. Comparative sequence analysis of mdh revealed that all V. cholerae O1 and O139 serogroup isolates belonged to the same clonal lineage. Single-strand conformational polymorphism (SSCP) analysis of these O1 and O139 strains at groEL confirmed the presence of an epidemic clonal complex. Of the 12 virulence regions examined, only three regions, Vibrio seventh pandemic island 1 (VSP-I), VSP-II, and RS1, were absent from all classical V. cholerae isolates. Most V. cholerae El Tor biotype and O139 serogroup isolates examined encoded all 12 virulence regions assayed. Outside of V. cholerae O1/O139 serogroup isolates, only one strain, VO7, contained VSP-I. Two V. cholerae El Tor isolates, GP155 and 2164-78, lacked both VSP-I and VSP-II, and one El Tor isolate, GP43, lacked VSP-II. Five non-O1/non-O139 serogroup isolates had an mdh sequence identical to that of the epidemic O1 and O139 strains. These isolates, similar to classical strains, lack both VSP-I and VSP-II. Four of the 12 virulence regions examined were found to be present in all isolates: hlyA, pilE, MSHA and RTX. Among non-O1/non-O139 isolates, however, the occurrence of the additional eight regions was considerably lower. The evolutionary relationships and multilocus virulence gene profiles of V. cholerae natural isolates indicate that consecutive pandemic strains arose from a common O1 serogroup progenitor through the successive acquisition of new virulence regions. 相似文献
72.
Summary We describe a technique using normal and diabetic (dbdb) mice to establish primary pancreatic cultures that spread and assume a characteristic epithelial morphology. These cultures contain 4 to 7% beta cells, secrete insulin in response to stimuli for 10 to 14 d, contain few fibroblasts, and have a cell viability that is greater than 95%. The cells attach firmly to glass cover slips and are ideal for the study of insulin secretory granules or contractile proteins using indirect immunofluorescence. 相似文献
73.
Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease 总被引:2,自引:0,他引:2
Janosíková B Pavlíková M Kocmanová D Vítová A Veselá K Krupková L Kahleová R Krijt J Kraml P Hyánek J Zvárová J Andel M Kozich V 《Molecular genetics and metabolism》2003,79(3):167-175
It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD. 相似文献
74.
Mireille Lahoud David Vremec Richard L. Boyd Ken Shortman 《Clinical & developmental immunology》1993,3(2):103-112
Thymic nurse cells (TNC), multicellular complexes consisting of lymphoid cells
enclosed within cortical epithelial cells, were isolated from mouse thymus by a modified
procedure allowing immunofluorescent labeling and flow cytometric analysis of their
lymphoid contents (TNC-L). Collagenase was the only protease used for tissue
digestion, to ensure that surface antigen markers remained intact. Zonal unit-gravity
elutriation was used to enrich the TNC on the basis of their high sedimentation rate,
followed by immunomagnetic bead depletion to remove residual mononuclear cell
contaminants and a density separation to remove debris. The TNC-L were then released
from inside TNC by a short period of culture. The measured contamination of TNC-L
with exogenous thymocytes was around 0.5%. Three-color immunofluorescent labeling
revealed that TNC-L included, as well as a maiority of immature CD4+8+3low thymocytes,
about 12% of apparently mature CD4+8-3high and CD4-8+3high thymocytes. TNC are
located in the cortex, where mature cells are rare; the occurrence of mature phenotype
cells within these structures suggests that they represent a microenvironment for the
selection and generation of mature T cells. 相似文献
75.
Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol 总被引:3,自引:0,他引:3
Bela Szabo Michal J. Urbanski Tiziana Bisogno Vincenzo Di Marzo Aitziber Mendiguren Wolfram U. Baer Ilka Freiman 《The Journal of physiology》2006,577(1):263-280
Endocannabinoids acting on CB1 cannabinoid receptors are involved in short- and long-term depression of synaptic transmission. The aim of the present study was to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG), is involved in depolarization-induced suppression of inhibition (DSI) in the cerebellar cortex, which is the most widely studied form of short-term depression. Depolarization of Purkinje cells in the mouse cerebellum led to an increase in intracellular calcium concentration and to suppression of the inhibitory input to these neurons (i.e. DSI occurred). Orlistat and RHC80267, two blockers of sn -1-diacylglycerol lipase, the enzyme catalysing 2-AG formation, abolished DSI by acting downstream of calcium influx. In contrast, DSI occurred also in the presence of a phospholipase C inhibitor. Intact operation of the calcium-dependent messengers calmodulin and Ca2+ –calmodulin-dependent protein kinase II were necessary for DSI. DSI was potentiated by an inhibitor of the main 2-AG-degrading enzyme, monoacylglycerol lipase. Interference with the anandamide metabolizing enzyme, fatty acid amide hydrolase, did not modify DSI. Thus, three kinds of observations identified 2-AG as the endocannabinoid involved in DSI in the mouse cerebellum: DSI was abolished by diacylglycerol lipase inhibitors; DSI was potentiated by a monoglyceride lipase inhibitor; and DSI was not changed by an inhibitor of fatty acid amide hydrolase. Further experiments indicated that 2-AG is the endocannabinoid mediating short-term retrograde signalling also at other synapses: orlistat abolished DSI in the rat cerebellum, DSI in the mouse substantia nigra pars reticulata and depolarization-induced suppression of excitation in the mouse cerebellum. 相似文献
76.
Heath EM Morken NW Campbell KA Tkach D Boyd EA Strom DA 《Archives of pathology & laboratory medicine》2001,125(1):127-133
CONTEXT: To maximize the participation rate in population genetic studies, alternatives to invasive whole blood collection are increasing. One such alternative is buccal epithelial cell collection, which, in contrast to venipuncture and finger sticks, is painless. Buccal cells, if collected and purified efficiently, offer an acceptable source for DNA to be used in research and clinical applications. OBJECTIVE: To develop a noninvasive sampling method for collecting cells for routine DNA testing in a clinical laboratory setting. DESIGN: Five factors were used to evaluate several brands of mouthwash: (1) compatibility with the DNA purification chemistry, (2) DNA yield, (3) DNA quality, (4) DNA stability at room temperature, and (5) mouthwash taste. Next, an optimization study was undertaken to maximize DNA yield. Finally, a validation study was undertaken with the optimized protocol to test a panel of 14 donors for DNA yield and performance and to test for the stability of DNA held in mouthwash. SETTING: Industrial research and development laboratory. RESULTS: Of 5 mouthwashes tested, Scope brand mouthwash received the highest overall ranking. The addition of proteinase K and glycogen to the protocol significantly enhanced DNA yields, with a test panel (n = 14) giving a range of 12 to 60 microg of DNA per donor. In a 4-week room temperature stability study, the DNA in mouthwash samples was found to be stable for at least 2 weeks. CONCLUSION: A clinically validated DNA purification chemistry was adapted to a noninvasive specimen collection method. This method used a commercially available mouthwash, Scope, to collect buccal epithelial cells for the preparation of high-quality DNA in high yield. 相似文献
77.
1. Active frog sartorius muscle in vitro liberates a substance into the bathing solution which has a pronounced stimulatory action on the frog heart.2. The stimulatory effect is not due to an increase in the K(+) concentration of the bathing solution, nor is it due to the liberation of catecholamines.3. In a molecular sieve chromatography procedure the stimulatory substance can be eluted in a single fraction which shows a maximum absorption of U.V. light at a wave-length of 265 nm, indicative of the presence of substances containing a purine ring.4. Low concentrations (10(-7)-10(-8) g/ml.) of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and uridine triphosphate (UTP) have a marked stimulatory action on the frog heart. The action of ATP and ADP on the heart is qualitatively very similar to that of the muscle bathing solution, while the action of UTP is distinctly different. The triphosphates of inosine, cytidine and guanosine stimulate the heart when in high concentration only. Adenosine and adenosine monophosphate do not stimulate the heart.5. Incubation of the muscle bathing solution and of solutions of ATP with the enzyme apyrase for the same time produces a similar marked reduction in the stimulatory action of both on the heart. Apyrase catalyses the break-down of nucleotide triphosphates to monophosphates.6. The elution behaviour of the stimulatory substance determined by molecular sieve chromatography is the same as that for ATP.7. The muscle bathing solution causes light to be emitted from firefly lantern extract, the pattern of light emission being similar to that produced by nucleotide triphosphates.8. The concentrations of ATP having the same quantitative action on the frog heart and on firefly extract as a given muscle bathing solution are almost identical, whereas the matching concentrations of ADP and UTP in the two methods of assay are widely different.9. It is concluded that ATP is released from active frog skeletal muscle in vitro. This release may play an important part in the reactive hyperaemia of muscular exercise since ATP has a powerful vasodilator action. 相似文献
78.
Sudo E Lee MM Boyd WA King M 《American journal of respiratory cell and molecular biology》2000,22(3):373-379
We compared the action of methacholine (MCh) and uridine 5'-triphosphate (UTP) with and without pretreatment with the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) on the transepithelial potential difference (PD), the mucus collection rate (MCR), and tracheal mucus rheology using anesthetized C57BL/6 mice. The cystic fibrosis transmembrane conductance regulator (CFTR) blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) was also used as a pretreatment for MCh. After collecting baseline mucus for 1.5 h, mucus secretion was stimulated by instilling 5 microl of 10(-2) M MCh or UTP around the upper trachea. There was a significant increase in PD after MCh or UTP stimulation (-21.3+/-2.0 mV MCh versus -14.1+/-1.6 mV control; -25.4+/-2.5 mV UTP versus -19.2+/-1.9 mV control). When UTP administration was preceded by DIDS, PD shifted from -15.2+/-2.9 to -12.0+/-2.2 mV. When MCh was preceded by DIDS or by NPPB, there was no change in PD. There was a significant decrease in mucus rigidity index, logG*, with MCh (2.54+/-0.09 versus 2.99+/-0.14 for control), similar to that previously reported in other species. With UTP, 14 of 16 mice responded in terms of PD becoming more negative, and of these, there was a significant difference in logG* after UTP administration (2.29 +/-0.10 versus 2.57+/-0.10 for control), whereas there was no change in logG* with DIDS administration before UTP. When DIDS administration preceded MCh, there was a diminished but still significant decrease in logG* from control, whereas there was no change in logG* when NPPB was preadministered. The control mucus collection rate was 0.19+/-0.09 mg/h, whereas after MCh stimulation, it increased to 2.83+/-0.78 mg/h. No significant difference was measured in the MCR after either UTP or DIDS+UTP stimulation. DIDS+MCh and NPPB+MCh both resulted in significant increases in MCR, but of a much smaller magnitude than that for MCh alone. We conclude that hypersecretion owing to UTP in C57BL/6 mice is less vigorous than with MCh, reflecting the limited population of Ca(2+)-dependent Cl(-) channels stimulated by UTP P(2) receptors. The action of MCh on tracheal mucus secretion in mice appears to involve both CFTR- and non-CFTR-dependent chloride channels. 相似文献
79.
Knowledge of HIV infection and AIDS, and attitudes to testing and counselling among general practitioners in Northern Ireland.
下载免费PDF全文
![点击此处可从《The British journal of general practice》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J S Boyd S Kerr R D Maw E A Finnighan P K Kilbane 《The British journal of general practice》1990,40(333):158-160
All 922 general practitioners in Northern Ireland were sent a questionnaire on human immunodeficiency virus (HIV) infection and the acquired immune deficiency syndrome (AIDS). Five hundred and ninety four general practitioners (64.4%) returned the questionnaire. Thirty eight respondents (6.4%) knew of an HIV positive patient in their practice and 93.3% felt they should be informed if one of their patients was found to be HIV positive at a genitourinary medicine clinic, even without the patient's consent. Of the respondents, 76.8% were willing to be involved in the management of AIDS patients in their practice in cooperation with hospital colleagues but only 37.5% felt confident to provide AIDS counselling and advice. Of the 368 general practitioners who did not feel confident to provide AIDS counselling and advice, 41.3% felt that they had insufficient knowledge and 79.6% felt uncertain of their counselling skills. The information gathered on the administration of injections, taking blood samples and disposal of needles indicated that further education for general practitioners is required to ensure safety at work. 相似文献
80.
The Competencies Conference: Future Directions in Education and Credentialing in Professional Psychology was held in Arizona in November 2002. One of the workshops, Individual and Cultural Differences (ICD), focused on racism, homophobia, and ageism. The consensus was that self-awareness and knowledge about the three "isms" are critical components in the education and training of psychologists. This article, authored by four of the workshop attendees, is a review of the current research and theoretical literature. Implications that address both content and context in graduate programs and training sites are presented. This is one of a series of articles published in this issue of the Journal of Clinical Psychology. Several other articles that resulted from the Competencies Conference will appear in Professional Psychology: Research and Practice and The Counseling Psychologist. 相似文献