全文获取类型
收费全文 | 15698篇 |
免费 | 909篇 |
国内免费 | 80篇 |
专业分类
耳鼻咽喉 | 108篇 |
儿科学 | 385篇 |
妇产科学 | 203篇 |
基础医学 | 2488篇 |
口腔科学 | 291篇 |
临床医学 | 1282篇 |
内科学 | 3311篇 |
皮肤病学 | 566篇 |
神经病学 | 1659篇 |
特种医学 | 615篇 |
外科学 | 2259篇 |
综合类 | 55篇 |
一般理论 | 7篇 |
预防医学 | 792篇 |
眼科学 | 488篇 |
药学 | 1102篇 |
中国医学 | 16篇 |
肿瘤学 | 1060篇 |
出版年
2023年 | 82篇 |
2022年 | 135篇 |
2021年 | 258篇 |
2020年 | 179篇 |
2019年 | 224篇 |
2018年 | 275篇 |
2017年 | 256篇 |
2016年 | 334篇 |
2015年 | 347篇 |
2014年 | 493篇 |
2013年 | 580篇 |
2012年 | 938篇 |
2011年 | 962篇 |
2010年 | 656篇 |
2009年 | 605篇 |
2008年 | 1057篇 |
2007年 | 1098篇 |
2006年 | 1092篇 |
2005年 | 1123篇 |
2004年 | 1006篇 |
2003年 | 940篇 |
2002年 | 923篇 |
2001年 | 283篇 |
2000年 | 197篇 |
1999年 | 232篇 |
1998年 | 223篇 |
1997年 | 154篇 |
1996年 | 139篇 |
1995年 | 128篇 |
1994年 | 91篇 |
1993年 | 112篇 |
1992年 | 89篇 |
1991年 | 87篇 |
1990年 | 84篇 |
1989年 | 80篇 |
1988年 | 100篇 |
1987年 | 76篇 |
1986年 | 69篇 |
1985年 | 62篇 |
1984年 | 55篇 |
1983年 | 58篇 |
1982年 | 68篇 |
1981年 | 39篇 |
1980年 | 45篇 |
1979年 | 38篇 |
1978年 | 42篇 |
1977年 | 42篇 |
1976年 | 39篇 |
1974年 | 39篇 |
1973年 | 36篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
91.
Jaroslava Ciesielski-Treska Jean-François Goetschy Gabrielle Ulrich Dominique Aunis 《Journal of neurocytology》1988,17(1):79-86
Summary Vimentin and glial fibrillary acidic protein (GFAP) represent the principal constituents of intermediate filaments found in astrocytes. In contrast to vimentin—GFAP transition which occurs during glial developmentin situ, vimentin coexists with GFAP in cortical astrocytes allowed to differentiate in culture. To examine whether culture conditions or proliferative activity of the cells is responsible for the expression of vimentin, we generated cultures of GFAP-positive, vimentin-negative astrocytes isolated from 26-day postnatal rat brain cortices. Isolated astrocytes are characterized by a very thin rim of perinuclear cytoplasm and by numerous processes. Antiserum to GFAP labelled major processes and cell somata of some astrocytes, especially those with relatively short and large processes. Within 3 days in culture, all astrocytes accumulated GFAP in hypertrophic cell bodies and many began to express vimentin. Vimentin appeared primarily close to nuclei, and filaments of vimentin extended into proximal segments of the cell processes. In some astrocytes, however, vimentin was always absent. Combined double immunolabelling and histoautoradiography experiments demonstrated that the acquisition of vimentin was independent of the ability of astrocytes to incorporate tritiated thymidine. The results indicate that astrocytes isolated from 26-day postnatal rat brain are heterogeneous with respect to their ability to express vimentin and that vimentin synthesis is not correlated with the growth state of the cells as had been previously suspected. 相似文献
92.
Somatoform pain disorder in the general population 总被引:6,自引:0,他引:6
Grabe HJ Meyer C Hapke U Rumpf HJ Freyberger HJ Dilling H John U 《Psychotherapy and psychosomatics》2003,72(2):88-94
BACKGROUND: Chronic pain disorder is assumed to represent a frequent and disabling condition. However, data on the prevalence of somatoform pain symptoms and somatoform pain disorder in the community are limited to date. METHODS: German versions of the Composite International Diagnostic Interview were administered to a representative national sample of 4,075 people. Somatoform pain disorder was diagnosed by standardized diagnostic algorithm based on the DSM-III-R criteria (absence of adequate physical findings). One subgroup was identified as also meeting the DSM-IV criterion B for 'significant distress or psychosocial impairment due to the somatoform pain'. RESULTS: A lifetime prevalence rate of somatoform pain disorder according to DSM-III-R of 33.7% and a 6-month rate of 17.3% was found. When applying the DSM-IV B criterion, the prevalence rate dropped to 12.3 and 5.4%, respectively. In both groups more than 95% of the probands had contacted their doctor because of the pain. In 25% of the probands the pain was positively assigned to psychological factors. A female:male ratio of 2:1 was found. CONCLUSIONS: Somatoform pain disorder (DSM-III-R) is a frequent condition. However, only about one third of these subjects is severely distressed or impaired by the pain. A clear operationalized concept of the DSM-IV criterion C 'psychological factors are judged to have an important role in the onset, severity, exacerbation or maintenance of the pain' should be provided in the further development of the diagnosis 'pain disorder' in order to make this diagnosis suitable for general population surveys. 相似文献
93.
Gerhold K Blümchen K Bock A Seib C Stock P Kallinich T Löhning M Wahn U Hamelmann E 《The Journal of allergy and clinical immunology》2002,110(1):110-116
BACKGROUND: Contact with immunomodulatory factors, such as LPS, in early infancy is associated with decreased allergen sensitization. OBJECTIVE: We sought to study the effects of systemic or airway exposure with LPS on the development of allergen sensitization, eosinophilic airway inflammation, and increased in vivo airway reactivity (AR) in a mouse model. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) plus adjuvant on days 1 and 14 and challenged through the airways with allergen on days 34 to 36. We performed measurement of OVA-specific IgE serum levels, in vitro T(H)2 cytokine production, differential cell counts in bronchoalveolar lavage fluids, and assessment of in vivo AR to inhaled methacholine by means of barometric whole-body plethysmography. RESULTS: Systemic LPS administration before OVA sensitization reduced OVA-specific IgE serum levels (426 +/- 76 vs 880 +/- 104 U/mL, P <.01), T(H)2 cytokine production by splenic mononuclear cells (IL-4: 0.08 +/- 0.01 vs 0.17 +/- 0.01 ng/mL; IL-5: 1.98 +/- 0.52 vs 4.11 +/- 0.54 ng/mL; P <.01), and extent of airway eosinophilia (total cell counts: 93 vs 376 x 10(3)/mL; eosinophils: 23% vs 51%; P <.01) compared with that in OVA-sensitized mice. Local LPS administration to sensitized mice before airway allergen challenges particularly induced IFN-gamma production by peribronchial lymph node cells in vitro (1718 +/- 315 vs 483 +/- 103 ng/mL, P <.01) associated with reduced airway eosinophilia compared with that seen in OVA-sensitized mice. Development of increased AR was not affected by systemic or local LPS exposure. Inhibitory effects of LPS on allergen sensitization and eosinophilic airway inflammation were inhibited by administration of anti-IL-12 antibodies before LPS exposure. CONCLUSION: These data indicate that local and systemic application of LPS modulates systemic and local T(H)1/T(H)2 immune responses in a distinct but similarly IL-12-dependent mode. 相似文献
94.
Identification and characterization of a conserved,stage-specific gene product of Plasmodium falciparum recognized by parasite growth inhibitory antibodies 下载免费PDF全文
Daubenberger CA Diaz D Curcic M Mueller MS Spielmann T Certa U Lipp J Pluschke G 《Infection and immunity》2003,71(4):2173-2181
We have identified a novel conserved protein of Plasmodium falciparum, designated D13, that is stage-specifically expressed in asexual blood stages of the parasite. The predicted open reading frame (ORF) D13 contains 863 amino acids with a calculated molecular mass of 99.7 kDa and displays a repeat region composed of pentapeptide motives. Northern blot analysis with lysates of synchronized blood stage parasites showed that D13 is highly expressed at the mRNA level during schizogony. The first N'-terminal 138 amino acids of D13 were expressed in Escherichia coli and the purified protein was used to generate anti-D13 monoclonal antibodies (MAbs). Using total lysates of blood stage parasites and Western blot analysis, these MAbs stained one single band of approximately 100 kDa, corresponding to the predicted molecular mass of ORF D13. Western blot analysis demonstrated further that D13 is expressed during schizogony, declines rapidly in early ring stages and is undetectable in trophozoites. D13 protein is localized in individual merozoites in a distinct area, as demonstrated by indirect immunofluorescence analysis. After subcellular fractionation, D13 was confined to the pelleted fraction of the parasite lysate and its extraction by alkaline carbonate buffer treatment indicated that D13 is not a membrane-integral protein. Inclusion of certain anti-D13 MAbs into in vitro cultures of blood stage parasites resulted in considerable reduction in parasite growth. The N'-terminal domain encompassing 158 amino acids is 94 and 95%, respectively, identical at the amino acid level between Plasmodium knowlesi, Plasmodium yoelii, and P. falciparum. In summary, we describe a novel stage-specifically expressed, highly conserved gene product of P. falciparum that is recognized by parasite growth inhibitory antibodies. 相似文献
95.
Zusammenfassung Um zu untersuchen, wie ein Tauch- oder Atemanhalte-manöver den Sauerstoffverbrauch und die CO2-Abgabe des Menschen beeinflußt, hielten 6 männliche Versuchspersonen 30, 60, 90, 120 und 165 sec ruhig an der Wasseroberfläche und an Land liegend den Atem an. In einer Vergleichsserie tauchten sie in 80 cm Tiefe gleich lange.Nach der Apnoe wurden der endexspiratorischeP
O
2 undP
CO
2, und die Sauerstoffaufnahme und die CO2-Abgabe pro Atemzug mit Hilfe eines Massenspektrometers und eines Pneumotachographen ermittelt.Es zeigte sich, daß die Sauerstoffschuld, die während der Apnoe eingegangen wird, beim Atemanhalten im Wasser bis zu 29%, an Land bis zu 38% unter der O2-Schuld lag, die zu erwarten wäre, wenn die gemessene Ruheaufnahme angehalten hätte. Beim Tauchen sank die O2-Schuld bis etwa 28% unter die erwartete Schuld. Der endexspiratorischeP
O
a in der ersten Exspiration fiel mit Zunahme der Apnoezeit ab, lag jedoch bei gleich langen Apnoezeiten nach Tauchen signifikant unter dem Wert nach Atemanhalten.Die CO2-Abgabe nach der Apnoe entsprach bis zu einer Apnoezeit von 90 sec etwa der in der Apnoe gebildeten Menge. Bei längeren Apnoezeiten trat eine deutliche CO2-Retention ein. Beim Atemanhalten wurde bis zu 60% weniger CO2 abgegeben als zu erwarten war.Der endexspiratorischeP
CO
2 im ersten Exspirationsgas lag unabhängig von der Apnoezeit ziemlich konstant bei 45 mm Hg, die CO2-Abgabe in der ersten Exspiration konstant bei etwa 150 ml ohne wesentlichen Unterschied zwischen Tauchen und Atemanhalten. 相似文献
96.
Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis 总被引:10,自引:0,他引:10 下载免费PDF全文
Yoshinobu Eishi Moritaka Suga Ikuo Ishige Daisuke Kobayashi Tetsuo Yamada Tamiko Takemura Touichiro Takizawa Morio Koike Shoji Kudoh Ulrich Costabel Josune Guzman Gianfranco Rizzato Marcello Gambacorta Ronald du Bois Andrew G. Nicholson Om P. Sharma Masayuki Ando 《Journal of clinical microbiology》2002,40(1):198-204
The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis. 相似文献
97.
Krueger S Kalinski T Hundertmark T Wex T Küster D Peitz U Ebert M Nägler DK Kellner U Malfertheiner P Naumann M Röcken C Roessner A 《The Journal of pathology》2005,207(1):32-42
Recently, we identified increased cathepsin X expression in H. pylori-infected gastric mucosa. Here, we describe further up-regulation in gastric cancer and report on the role of inflammatory cytokines required for cathepsin X up-regulation in H. pylori-infected gastric mucosa, as well as on consequences for cellular invasion. Biopsy specimens were taken from the antrum, corpus and cardia of H. pylori-infected and non-infected patients. Gastric cancer samples were obtained from patients undergoing gastric surgery. Cathepsin X was detected in gastric mucosa by quantitative real-time RT-PCR, western blotting and immunohistochemistry. Induction of cathepsin X expression in epithelial and inflammatory cells caused by H. pylori infection was tested in in vitro contact and non-contact co-cultures of AGS cells and monocytic cells. Patients with H. pylori gastritis showed significantly higher cathepsin X mRNA (2.5-fold) and protein (1.6-fold) expression than H. pylori-negative patients. Cathepsin X was also up-regulated in gastric cancer (3-12-fold) compared to non-neoplastic mucosa. Cathepsin X was predominantly expressed by macrophages in the mucosal stroma and in glands of the antral mucosa. In addition, tumour cells stained for cathepsin X in 26 (68%) patients with gastric carcinoma. In general, staining was significantly more common (20 vs. 6 patients) and more intense (3.55 vs. 0.83) in intestinal type gastric cancer than in the diffuse type. In vitro cell culture experiments revealed that intercellular signalling between pathogenicity island (PAI)-positive H. pylori-infected epithelial cells and macrophages via soluble factors in the culture medium seems to be responsible for increased expression of cathepsin X in monocytes. Using antisense oligonucleotides, cathepsin X up-regulation was directly associated with higher invasiveness in vitro. Although no correlation of cathepsin X expression and TNM stage was found, our study demonstrates that cathepsin X plays a role not only in the chronic inflammation of gastric mucosa but also in the tumourigenesis of gastric cancer. 相似文献
98.
Elisabetta Padovan Tanja Bauer Marie Marte Tongio Hubert Kalbacher Hans Ulrich Weltzien 《European journal of immunology》1997,27(6):1303-1307
Although hapten immune responses have been intensively studied in the mouse, very little is known about hapten determinants involved in human allergic reactions. Penicillins, as chemically reactive compounds of low molecular weight, constitute typical examples of hapten allergens for humans. Penicillins become immunogenic only after covalent binding to carrier proteins and in this form frequently induce IgE-mediated allergic reactions in patients subjected to antibiotic treatment. However, our previous data strongly indicated that penicillins also form part of the epitopes contacting the antigen receptors of beta lactam-specific T cells in allergic individuals. We have therefore investigated the molecular constraints involved in the T cell immune response to penicillin G (Pen G). Designer peptides containing a DRB1*0401-binding motif and covalently modified with Pen G via a lysine σ-amino group were found to induce proliferation of Pen G-specific T cell clones. A precise positioning of the hapten molecule on the peptide backbone was required for optimal T cell recognition. Furthermore, we extended these observations from our designer peptides to show that a peptide sequence derived from a natural DRB1*1101-binding peptide modified in vitro with Pen G, also acquired antigenic properties. Our data for the first time provide insight into the manner in which allergenic haptens are recognized by human T cells involved in allergic reactions to drugs and suggest possible mechanisms leading to the onset of these adverse immune responses. 相似文献
99.
Daniel Lamontagne Ulrich Pohl Rudi Busse 《Pflügers Archiv : European journal of physiology》1991,418(3):266-270
The effects of a recently described inhibitor of endothelial NO synthesis, N
G-nitro-l-arginine (l-NNA), on the vasomotor responses to endothelium-dependent and independent vasodilators, and on the release of endothelium-derived relaxing factor (EDRF), were studied in the isolated saline-perfused rabbit heart. Infusion of l-NNA (30 M) resulted in a 52±12% increase in basal coronary perfusion pressure. The vasomotor responses to 1 M acetylcholine (ACh) and serotonin after l-NNA became biphasic, showing a small transient dilation followed by a pronounced vasoconstriction. In contrast, the dilation observed with sodium nitroprusside was not affected by l-NNA. None of the above-mentioned effects was elicited by the Stereo-isomer d-NNA. Similarly, an increase in the basal coronary perfusion pressure by endothelin-1 (0.3 nM) to the same level as observed with l-NNA did not alter the vasomotor responses to ACh and sodium nitroprusside. The increase in cyclic GMP (cGMP) in platelets passing through the coronary vascular bed was used as an index of EDRF release. Platelet cGMP amounted to 0.50±0.10 pmol/mg protein after passage through the coronary bed of the unstimulated heart. When platelets were injected during an ACh infusion (1 M), a 2.7 fold increase in cGMP was observed (P<0.01). After a 30-min infusion with l-NNA, the cGMP content of platelets passing through the unstimulated heart was reduced by 62%. Likewise, the ACh-induced increase in platelet cGMP was totally blocked. These results show that l-NNA inhibits EDRF release, and is thus a potent and selective inhibitor of EDRF-mediated dilation in the isolated rabbit heart. 相似文献
100.
Marion Dorsch Hanno Hock Ulrich Kunzendorf Tibor Diamantstein Thomas Blankenstein 《European journal of immunology》1993,23(1):186-190
In order to analyze the effect of a high local concentration of macrophage colony-stimulating factor (M-CSF; CSF-1) on tumor growth, the plasmacytoma cell line J558L was transfected with the human M-CSF gene and injected into syngeneic BALB/c mice. In contrast to the parental tumors, M-CSF transfectants were heavily infiltrated by macrophages as evidenced by immunohistochemistry with antibodies to Mac-1 and Mac-3 and by isolation of the macrophages from the tumor. Nevertheless, tumor growth was only slightly affected by M-CSF and M-CSF-producing cells grew as tumor in all cases. The growth retardation of M-CSF-producing cells varied depending on the experiment and seemed to be due to an indirect effect because the growth rate of the cells in vitro had not changed upon gene transfer. Attempts to activate the tumor-infiltrating macrophages for tumor suppression by systemic application of interferon-γ and/or lipopolysaccharide were not successful. Altogether, our results suggest that M-CSF is a potent chemoattractant for macrophages in vivo but alone is not sufficient to activate these macrophages for tumoricidal activity. 相似文献