全文获取类型
收费全文 | 8532篇 |
免费 | 353篇 |
国内免费 | 52篇 |
专业分类
耳鼻咽喉 | 79篇 |
儿科学 | 168篇 |
妇产科学 | 110篇 |
基础医学 | 1384篇 |
口腔科学 | 155篇 |
临床医学 | 740篇 |
内科学 | 2084篇 |
皮肤病学 | 116篇 |
神经病学 | 681篇 |
特种医学 | 252篇 |
外科学 | 1142篇 |
综合类 | 64篇 |
一般理论 | 3篇 |
预防医学 | 502篇 |
眼科学 | 110篇 |
药学 | 625篇 |
中国医学 | 10篇 |
肿瘤学 | 712篇 |
出版年
2023年 | 24篇 |
2022年 | 44篇 |
2021年 | 144篇 |
2020年 | 74篇 |
2019年 | 98篇 |
2018年 | 104篇 |
2017年 | 83篇 |
2016年 | 90篇 |
2015年 | 144篇 |
2014年 | 208篇 |
2013年 | 281篇 |
2012年 | 529篇 |
2011年 | 546篇 |
2010年 | 300篇 |
2009年 | 310篇 |
2008年 | 549篇 |
2007年 | 602篇 |
2006年 | 626篇 |
2005年 | 695篇 |
2004年 | 636篇 |
2003年 | 654篇 |
2002年 | 553篇 |
2001年 | 104篇 |
2000年 | 86篇 |
1999年 | 121篇 |
1998年 | 166篇 |
1997年 | 123篇 |
1996年 | 108篇 |
1995年 | 87篇 |
1994年 | 111篇 |
1993年 | 80篇 |
1992年 | 55篇 |
1991年 | 43篇 |
1990年 | 51篇 |
1989年 | 34篇 |
1988年 | 43篇 |
1987年 | 40篇 |
1986年 | 43篇 |
1985年 | 41篇 |
1984年 | 30篇 |
1983年 | 24篇 |
1982年 | 44篇 |
1981年 | 44篇 |
1980年 | 33篇 |
1979年 | 16篇 |
1978年 | 24篇 |
1977年 | 18篇 |
1976年 | 10篇 |
1974年 | 10篇 |
1973年 | 14篇 |
排序方式: 共有8937条查询结果,搜索用时 46 毫秒
91.
Pierre Moine Colette Sauve Eric Vallee Jean-Pierre Bedos Esther Azoulay-Dupuis 《Clinical microbiology and infection》1997,3(6):608-615
Objective: To compare cefotaxime (CTX) to amoxicillin (AMO) (usually considered the definitive therapy for penicillinsusceptible Streptococcus pneumoniae infections) in an immunocompromised mouse pneumonia model.
Methods: Three S. pneumoniae clinical isolates were used: two serotype 19 strains, a penicillin-susceptible (Ps ) strain (penicillin MIC = 0.03 μ/mL) and a highly penicillin-resistant (Pr ) strain (penicillin MIC = 4 μ/mL), and one serotype 23F strain, a penicillin-cephalosporin-resistant (CFTR) strain (CTX MIC = 4 μ/mL).
Results: CTX activity in this mouse model of pneumonia induced by the highly penicillin-resistant strain of S. pneumoniae was lower than expected from its low MIC against this organism. Furthermore, AMO had greater efficacy than CTX against a CFTR S. pneumoniae strain.
Conclusion: Our data suggest that there is no major difference in the in vivo efficacy of the two agents, cefotaxime and amoxicillin, against penicillin-resistant and penicillin-cephalosporin-resistant S. pneumoniae. 相似文献
Methods: Three S. pneumoniae clinical isolates were used: two serotype 19 strains, a penicillin-susceptible (P
Results: CTX activity in this mouse model of pneumonia induced by the highly penicillin-resistant strain of S. pneumoniae was lower than expected from its low MIC against this organism. Furthermore, AMO had greater efficacy than CTX against a CFTR S. pneumoniae strain.
Conclusion: Our data suggest that there is no major difference in the in vivo efficacy of the two agents, cefotaxime and amoxicillin, against penicillin-resistant and penicillin-cephalosporin-resistant S. pneumoniae. 相似文献
92.
M Issa A Buemi L J Holderbach A Ratignier D Laedlein-Greilsammer J Sengler 《Journal de chirurgie》1984,121(6-7):425-429
The authors describe two cases of non parasitic cyst of the spleen of "enteroid" origin on histological examination. No similar cases have yet seen described in the medical literature that we consulted. The histology of these two cases is quite unusual in that cysts are multilocular and mucoid with a cylindrical mucus secreting epithelium similar to cystic tumours of the ovary. The outcome of the first case remains favorable four years after surgery. As in the case of mucoid or enteroid cyst of the ovary, a disembryological origin seems the most likely explanation of these cyst of the spleen. 相似文献
93.
94.
95.
Jean-Claude Brouet William Vainchenker Dominique Blanchard Ugo Testa Jean-Pierre Cartron 《European journal of immunology》1983,13(4):350-352
The Tn (or polyagglutinability) syndrome corresponds to a human nonmalignant acquired condition which results from a somatic mutation occurring at the level of bone marrow stem cells. This model offers therefore a unique opportunity to study the contribution of multipotential stem cells to the maintenance of cells from the lymphoid lineage. We found that the Tn mutation is expressed by both myeloid and lymphoid mature blood cells. Whereas a large proportion of surface IgM-bearing B cells carry the Tn mutation, only a small percentage of T cells and IgA- or IgG-bearing B cells are defective, showing that under physiological conditions the penetration of stem cells into the various myeloid and lymphoid compartments is variable. 相似文献
96.
Jean-Pierre Laussac 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1990,12(1):37-54
Thymulin (formerly called FTS) is a well-defined nonapeptide hormone produced by thymic epithelial cells. Its biological activity and antigenicity depend on the presence of the metal zinc in the molecule. The interaction between this metal ion and thymulin has been investigated by means of one- and two-dimensional NMR experiments. These experiments were performed in dimethyl-d 6 sulfoxide solution and in aqueous medium with different metal: peptide ratios. The results are compared with those obtained for complexes of thymulin with other metal ions (Cu2+ and Al3+) and for the [Ala4]- and [Ala8]-analogs in terms of biological activity. These comparative studies suggest that the 1∶1 complex is the only conformation recognized by the antibodies. From the NOESY data, a spatial conformation has been proposed for this complex. This conformation should be the physiological one and could lead to a better insight into the conformation requirements at receptor sites. 相似文献
97.
Issa Loutfi Patricia M. Chisholm Debbie Bevan John P. Lavender 《European journal of nuclear medicine and molecular imaging》1990,16(2):69-76
An indium 111-labelled mouse anti-rat T cell monoclonal antibody, MRC OX-19, was injected intravenously into rats to establish the usefulness of radiolabelled anti-lymphocyte antibodies in imaging lymphoid tissues. Antibody binding in vivo, measured by immunofluorescence analysis of cell suspensions made from lymphoid tissues, was detectable on lymphocytes in blood, spleen and lymph nodes. The extent of binding was time and antibody-dose dependent. Doses of antibody above 80 g/kg body weight resulted in modulation, i.e. loss of CD 5 (T 1) molecules from the cell surface, although the cells remained in the circulation. Modulation was demonstrable within 2 h and for at least 24 h after a single injection of antibody. Intravenous injection of111In-MRC OX-19 resulted in levels of in vivo binding comparable with those seen with unlabelled antibody. Scintillation imaging showed early splenic localisation persisting over 48h, a more gradual localisation in the lymph nodes seen clearly at 24 h and a steady background. Comparison of the in vivo distribution of labelled antibody and111In-tropolone-labelled lymphocytes showed that both could be used for external imaging of lymphocytes by scintillation camera. 相似文献
98.
Hideki Morimoto Paola Princine Jean-Pierre Robin Colette Broquet Jean Michel Mencia-Huerta Pierre Braquet Benjamin Bonavida 《Cancer chemotherapy and pharmacology》1993,32(4):293-300
The in vitro cytotoxic properties of a newly synthesized demethylpodophyllotoxin derivative, 4-o-butanoyl-4-demethylpodophyllotoxin (BN 58705), were determined by using several human tumor cell lines of different histological origin and of different sensitivity to conventional chemotherapeutic drugs (Adriamycin andcis-diammine-dichloride platinum). BN 58705 is shown to be cytotoxic against various human tumor cell lines as assessed by the MTT assay. Furthermore, BN 58705 is shown to be cytotoxic against several drug-resistant tumor cell lines. BN 58705 is cytotoxic at concentrations 100- to 1000-fold lower than those of Adriamycin orcis-diammine-dichloride platinum required to achieve similar cytotoxicity. BN 58705 did not mediate DNA fragmentation of target cells, whereas the epipodophyllotoxin-like etoposide induced DNA cleavage by stabilizing the DNA-enzyme intermediate. Like vinca alkaloids, BN 58705 induced a block in the mitotic phase of the cell cycle. By comparison, BN 58705 exerted a stronger cytotoxic activity in vitro than did either etoposide, an epipodophyllotoxin, or vincristine, a vinca alkaloid. When BN 58705 was applied in vivo in mice, it resulted in low toxicity (50% lethal dose, 150 mg/kg). These results demonstrate than BN 58705 is cytotoxic to drug-resistant human tumor cell lines and is manyfold more potent than conventional drugs. The cytotoxic potency and low toxicity of BN 58705 are important criteria to establish its potential chemotherapeutic efficacy in vivo.Abbreviations cpm
counts per minute
- BN 58705
4-o-butanoyl-4-demethylpodophyllotoxin
- MTT
3-(4,5-dimethyl-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide
- OD
optical density
- TRIS
TRIS (hydroxymethyl) aminomethane
- EDTA
ethylenediaminetetraacetic acid
- FITC
fluoresceinisothiocyanate
- PI
propidium iodide
This work was supported by a grant from Institut Henri Beaufour, France 相似文献
99.
Tiziano Croci Marco Landi Danielle Gully Jean-Pierre Maffrand Gérard Le Fur Luciano Manara 《British journal of pharmacology》1997,120(7):1312-1318
- We investigated the effect of the non-peptide neurotensin (NT) antagonist SR 48692 on renal function in rats and the involvement of nitric oxide (NO) in the diuretic action of this compound.
- In fed animals, SR 48692 dose-dependently (0.5 to 12.5 mg kg−1, p.o., 0.03 to 1 mg kg−1, i.p. and 0.1 to 1 μg/rat, i.c.v.) increased urine output and urinary excretion of Na+, K+ and Cl− and reduced urine osmolality. The diuretic activity was also evident in water-deprived, fasted animals and in fasted, water-loaded rats.
- NT (0.1 μg/rat, i.c.v.) had no effect on urine output in fed rats, but reduced the diuretic action of SR 48692 (1 μg/rat, i.c.v.). The opposite result was obtained in fasted, water-loaded animals: NT dose-dependently (0.01 and 0.1 μg/rat, i.c.v.) inhibited diuresis and this effect was significantly inhibited by i.c.v. SR 48692. In this experimental condition, SR 48692 did not further increase the on-going diuresis.
- The NO synthesis inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 30 mg kg−1, i.p.) alone had no effect on urine output in fed rats but prevented the diuretic action of i.c.v. or i.p. SR 48692; L-arginine (1 g kg−1, i.p.) but not D-arginine (1 g kg−1, i.p.) restored the SR 48692-dependent increase in diuresis. L-NAME had no effect on furosemide-stimulated diuresis.
- Systemically administered L-NAME or i.c.v. NT in fasted, water-loaded rats significantly reduced water diuresis but this effect was no longer seen in animals given i.p. L-arginine. Rats receiving i.c.v. NT, whose diuresis was significantly reduced, also excreted less nitrates and nitrites in urine.
- Increased diuresis after central or systemic administration of SR 48692 to fed rats was paralleled by increased urinary excretion of nitrates and nitrites, this being consistent with peripheral enhancement of NO production after NT-receptor blockade by SR 48692. The increase in diuresis after furosemide also involved an increase of nitrates and nitrites in urine, but this effect was about half that attained with an equipotent diuretic dose of SR 48692.
- In fed rats, the NO donor isosorbide-dinitrate, reduced systolic blood pressure (unlike SR 48692 which did not affect blood pressure) but also dose-dependently (1 and 5 mg kg−1, i.p.) stimulated urine output.
- The overall effects of SR 48692 strongly support a link between the actions of endogenous NT, AVP and peripheral NO production in the modulation of renal excretion of water, Na+, K+ and Cl−.
100.
Tumor necrosis factor-{alpha} up-regulates Bcl-2 expression and decreases calcium-dependent apoptosis in human B cell lines 总被引:7,自引:0,他引:7
Genestier Laurent; Bonnefoy-Berard Nathalie; Rouault Jean-Pierre; Flacher Monique; Revillard Jean-Pierre 《International immunology》1995,7(4):533-540
Group I and Epstein–Barr virus-negative Burkitt's lymphomacell lines and the B104 lymphoma cell line which expresses aphenotype of immature B cells undergo apoptosis after cross-linkingof their surface Ig receptors or after exposure to a calciumionophore. We show here that tumor necrosis factor (TNF)- protectsthese B cell lines against Ca2+-dependent apoptosis. Protectionwas associated with up-regulatlon of bcl-2 mRNA and proteinexpression. The increase of Bcl-2 expression induced by TNF-was inhibited by chelerythrine, a specific inhibitor of proteinkinase C (PKC), suggesting that Bcl-2 expression was dependenton PKC activation. Furthermore, we show that phorbol estersand cyclosporin A (CsA), which prevent Ca2+-dependent apoptosis,up-regulated Bcl-2 expression. The effect of CsA on Bcl-2 expressionis controlled by calcineurin since we have shown that FK506but not rapamycin had the same effect on Bcl-2 expression, whereasokadaic acid, an inhibitor of phosphatases 1, 2A and 2C, wasineffective. These data provide direct evidence that TNF- preventsCa2+-dependent apoptosis by a Bcl-2-dependent mechanism mediatedby PKC. 相似文献