全文获取类型
收费全文 | 2799篇 |
免费 | 222篇 |
国内免费 | 37篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 79篇 |
妇产科学 | 43篇 |
基础医学 | 311篇 |
口腔科学 | 122篇 |
临床医学 | 629篇 |
内科学 | 566篇 |
皮肤病学 | 22篇 |
神经病学 | 257篇 |
特种医学 | 157篇 |
外科学 | 181篇 |
综合类 | 61篇 |
预防医学 | 183篇 |
眼科学 | 25篇 |
药学 | 284篇 |
中国医学 | 7篇 |
肿瘤学 | 119篇 |
出版年
2021年 | 18篇 |
2019年 | 30篇 |
2018年 | 44篇 |
2017年 | 17篇 |
2016年 | 19篇 |
2015年 | 40篇 |
2014年 | 42篇 |
2013年 | 75篇 |
2012年 | 82篇 |
2011年 | 73篇 |
2010年 | 55篇 |
2009年 | 69篇 |
2008年 | 70篇 |
2007年 | 86篇 |
2006年 | 89篇 |
2005年 | 75篇 |
2004年 | 95篇 |
2003年 | 90篇 |
2002年 | 70篇 |
2001年 | 105篇 |
2000年 | 89篇 |
1999年 | 104篇 |
1998年 | 117篇 |
1997年 | 107篇 |
1996年 | 100篇 |
1995年 | 80篇 |
1994年 | 59篇 |
1993年 | 81篇 |
1992年 | 71篇 |
1991年 | 81篇 |
1990年 | 73篇 |
1989年 | 69篇 |
1988年 | 80篇 |
1987年 | 61篇 |
1986年 | 68篇 |
1985年 | 66篇 |
1984年 | 57篇 |
1983年 | 29篇 |
1982年 | 22篇 |
1981年 | 27篇 |
1980年 | 21篇 |
1979年 | 42篇 |
1978年 | 33篇 |
1977年 | 17篇 |
1975年 | 20篇 |
1974年 | 26篇 |
1972年 | 19篇 |
1970年 | 18篇 |
1969年 | 21篇 |
1968年 | 17篇 |
排序方式: 共有3058条查询结果,搜索用时 31 毫秒
21.
22.
Nancy J. Fishwick RN PhD CS 《Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG》1998,27(6):661-670
Nearly 4 million women in the United States were physically hurt by their husbands or boyfriends in 1994. The health and well-being of these women and their children, as well as the women who are overlooked in these statistics, are jeopardized by past and current experiences with abuse within intimate relationships. Strategies for nurses in women's health care settings to screen women for current or past abuse within their intimate personal relationships, guidelines for effective responses to disclosure of abuse, and supportive interventions are described. 相似文献
23.
24.
25.
26.
Peter Cutler 《Health economics》1993,2(1):65-75
In this paper it is shown that there have been significant structural changes in the composition of the Hospital and Community Health Services (HCHS) workforce over the 1980s. The number of doctors, nurses and other medical professionals has grown at the expense of support staff such as ancillaries and maintenance workers. The number of agency and contract staff has risen rapidly, partly offsetting the loss of directly-employed support staff. Changes in the workforce have been compared with changes in activity, as measured by the cost-weighted activity index. According to this measure labour productivity has grown by a compound rate of 1.9% annually. Adjusting the labour force index for the wage bill of each group reveals productivity growth of 1.5%. The effectiveness of treatment, as proxied by the decline in avoidable perinatal mortality, has grown by 3.4% annually. Unit labour costs have fallen over the period at an average annual rate of 0.3%. The trend conceals wide fluctuations, with labour costs falling slowly during the first half of the decade, and rising strongly during the second half. Medical professionals benefited disproportionately from wage increases in comparison with other HCHS groups during the mid to late 1980s. 相似文献
27.
In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances. 相似文献
28.
Amy C. Fuchs Eric V. Granowitz Leland Shapiro Edouard Vannier Gerhard Lonnemann Jonathan B. Angel Jeffrey S. Kennedy Arthur R. Rabson Elaine Radwanski Melton B. Affrime David L. Cutler Paul C. Grint Charles A. Dinarello 《Journal of clinical immunology》1996,16(5):291-303
We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25g/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15±1.1, 208±20.1, and 505±22.3 ng/ml) occurred after 2–5 min for 1, 10, and 25g/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24–63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12–24%) in neutrophil superoxide generation. There was a marked inhibition (60–95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10g/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72–87%) in interferon- (IFN) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reducesex vivo production of IL-6, IL-8, and IFN. 相似文献
29.
Cloning of the nitrate reductase gene of Stagonospora (Septoria) nodorum and its use as a selectable marker for targeted transformation 总被引:1,自引:0,他引:1
The nitrate reductase gene (NIA1) of the phytopathogenic fungus Stagonospora (Septoria) nodorum has been cloned from a cosmid library by homologous hybridisation with a PCR-generated probe. A 6.7-kb fragment carrying
the NIA1 gene was subcloned and partially characterised by restriction mapping. Sequencing of the gene indicated a high degree of
homology, both at the nucleotide and amino-acid levels, with nitrate reductase genes of other filamentous fungi. Furthermore,
consensus regulatory signals thought to be involved in the control of nitrogen metabolism are present in the 5′ flanking region.
The cloned NIA1 gene has been used to develop a gene-transfer system based on nitrate assimilation. Stable nia1 mutants of S. nodorum defective in nitrate reductase were isolated by virtue of their resistance to chlorate. These were transformed back to nitrate
utilisation with the wild-type S. nodorum NIA1 gene. Southern analyses revealed that transformation occurred as a result of the integration of transforming DNA into the
fungal genome; in all cases examined, integration was targeted to the homologous sequence.
Received: 30 March / 9 June 1998 相似文献
30.
Mason X. Zhang Jim E. Cutler Yongmoon Han Thomas R. Kozel 《Infection and immunity》1998,66(12):6027-6029
Polyclonal antimannan immunoglobulin G (IgG) activates the classical complement pathway and accelerates initiation of the alternative pathway by Canidida albicans. This dual role was assessed for two antimannan IgM monoclonal antibodies (MAbs). MAb B6.1 is specific for an epitope on the acid-labile portion of C. albicans phosphomannan; MAb B6 is specific for an epitope on the acid-stable region. Both MAbs were potent activators of the classical pathway but poor facilitators of alternative pathway initiation.Candida albicans activates the human complement system via both the classical and the alternative pathways, leading to deposition of opsonic complement fragments on the yeast cell surface (8, 10, 18). In previous studies, we described a critical role for naturally occurring antimannan immunoglobulin G (IgG) in complement activation by C. albicans. Those studies used a kinetic assay for C3 deposition on the yeast and immunofluorescence evaluation of the sites of C3 binding (10, 17, 18). Deposition of C3 onto C. albicans cells incubated in normal human serum (NHS) occurs rapidly via the classical pathway and can be detected within the first 2 min of incubation. If the classical pathway is blocked by chelation of Ca2+ with EGTA, C3 deposition occurs via the alternative pathway, but C3 deposition is delayed and a 6-min incubation is required before bound C3 is readily detectable on the yeast surface. Removal of naturally occurring antimannan IgG from the serum by mannan absorption profoundly delays accumulation of C3 on the yeast cell surface, with 12 min or more of incubation being required before appreciable amounts of bound C3 are detected. However, this 12-min delay can be overcome by supplementation of the mannan-absorbed serum with affinity-purified human antimannan IgG in the absence of EGTA to mediate classical pathway initiation or shortened to 6 min in the presence of EGTA to allow antibody-facilitated activation of the alternative pathway. These observations demonstrate a dual role for antimannan IgG in serum from healthy adults in complement activation by C. albicans. Antimannan IgG mediates activation of the classical pathway and facilitates initiation of the alternative pathway (17, 18).In studies described above, we used polyclonal antimannan IgG purified from pooled human plasma. Since C. albicans cells express a number of immunodominant mannan components recognized by rabbits (15, 16), the human polyclonal antimannan IgG likely contains a range of specificities for distinct mannan determinants. It has been shown that rabbit antibodies that are reactive with three different cell wall determinants of group A streptococci display differential abilities to activate the classical or alternative pathway (2). Although the antibodies specific for three different cell wall epitopes all activated the classical pathway, only antibody specific for the N-acetyl-d-glucosamine epitope activated the alternative pathway (2). In a separate study, capsular as well as noncapsular antibodies were found to direct classical-pathway-mediated killing of Haemophilus influenzae type b, whereas only the capsular antibodies promoted killing by the alternative pathway (12). These studies provide evidence that epitope specificity may influence the ability of an antibody to activate the alternative pathway and prompted us to examine whether antibodies that recognize different mannan determinants are able to mediate activation of the classical and alternative pathways by C. albicans.Two IgM monoclonal antibodies (MAbs) that recognize distinct mannan determinants were compared for their abilities to activate the classical or alternative pathway. MAb B6.1 is specific for an acid-labile component of the Candida phosphomannan complex, and MAb B6 is specific for an acid-stable component (5). The MAbs were produced commercially (Montana ImmunoTech, Inc., Bozeman, Mont.).C. albicans CA-1 was grown as yeast forms to stationary phase in glucose (2%)-yeast extract (0.3%)-peptone (1%) broth for 24 h at 37°C as described elsewhere (4, 6, 10). The mannan of CA-1 yeast was purified as described previously (7, 18) and coupled to CNBr-Sepahrose 4B (Pharmacia Biotech, Uppsala, Sweden) (18).Pooled NHS was prepared from peripheral blood from at least 10 healthy adult donors and stored at −80°C. C3 was isolated from frozen human plasma (9, 13) and stored at −80°C until used. C3 was labeled with 125I as described previously (3) by use of IODO-GEN reagent (Pierce, Rockford, Ill.). NHS was absorbed with mannan-Sepharose 4B to remove antimannan antibodies (18).Kinetics of C3 binding were assayed by the method of Kozel et al. (10). To determine whether MAb B6 or B6.1 activates the classical pathway, 2 × 106 yeast cells were incubated at 37°C in 1 ml of a complement binding medium that contained (i) 40% NHS, mannan-absorbed serum, or mannan-absorbed serum supplemented with MAb B6 or B6.1, (ii) sodium Veronal (5 mM)-buffered saline (142 mM, pH 7.3) containing 0.1% gelatin, 1.5 mM CaCl2, and 1 mM MgCl2, and (iii) 125I-labeled C3. To study whether MAb B6 or B6.1 plays a role in alternative pathway initiation, yeast cells were incubated in the manner described above except that the binding medium was not supplemented with Ca2+ and contained 5 mM EGTA and 5 mM MgCl2. At various time intervals from 2 to 16 min, 50-μl samples were withdrawn in duplicate and added to 200 μl of phosphate-buffered saline–0.1% sodium dodecyl sulfate–20 mM EDTA in Millipore MABX-N12 filter plates fitted with BV 1.2-μm-pore-size filter membranes (Millipore, Bedford, Mass.). The cells were washed with phosphate-buffered saline–0.1% sodium dodecyl sulfate, and filter-bound radioactivity was determined with a gamma counter. Nonspecific binding was estimated from cells incubated in NHS containing EDTA and was subtracted from the total counts.Mannan absorption of serum profoundly delayed C3 accumulation on yeast from 2 min to approximately 10 min (Fig. (Fig.11 and and2).2). However, addition of either MAb B6 or MAb B6.1 at 50 μg per ml of reaction mixture to the absorbed serum generated rapid activation kinetics characteristic of C3 deposition via the classical pathway (Fig. (Fig.1)1) (10, 17, 18). This observation was not unexpected, as polyvalent IgM is known to be a potent activator of the classical pathway. Open in a separate windowFIG. 1Effect of MAb B6 or B6.1 on the kinetics of C3 deposition on C. albicans cells via the classical pathway. Yeast cells were incubated in a C3 binding medium containing (i) 40% NHS (•), (ii) 40% mannan-absorbed NHS (○), (iii) 40% mannan-absorbed NHS supplemented with MAb B6 (▴), or (iv) 40% mannan-absorbed NHS supplemented with MAb B6.1 (▿) at 50 μg per ml of reaction mixture. C3 deposition patterns from three independent assays were similar; results from one representative assay are shown.Open in a separate windowFIG. 2Effect of MAb B6 or B6.1 on the kinetics of C3 deposition on C. albicans cells via the alternative pathway. Yeast cells were incubated in a C3 binding medium containing (i) 40% NHS (•), (ii) 40% NHS–EGTA (■), (iii) 40% mannan-absorbed NHS containing EGTA (○), (vi) 40% mannan-absorbed NHS containing EGTA supplemented with MAb B6 (▴), or (iv) 40% mannan-absorbed NHS supplemented with MAb B6.1 (▿) at 50 μg per ml of reaction mixture. C3 deposition patterns from four independent assays were similar; results from one representative assay are shown.The effects of MAbs B6 and B6.1 on activation of the alternative pathway were assessed by addition of the antibodies to mannan-absorbed serum in the presence of EGTA. The results (Fig. (Fig.2)2) showed that neither MAb B6 nor MAb B6.1 at 50 μg per ml of reaction mixture altered the alternative pathway activity of the mannan-absorbed serum. To determine whether the inability of MAb B6 or B6.1 to facilitate initiation of the alternative pathway was influenced by antibody concentration, the experiment represented in Fig. Fig.22 was repeated with mannan-absorbed serum that was supplemented with 10 to 160 μg of MAb B6 or B6.1 per ml. These antibody concentrations were chosen because in our previous studies we found that affinity-purified human antimannan IgG activates both the classical and alternative pathways (17). However, at 10, 40, or 160 μg per ml of reaction mixture, both antibodies failed to enhance alternative pathway activity of mannan-absorbed serum but promoted classical pathway activity (data not shown).The observation that both MAbs were unable to enhance alternative pathway activity was unexpected. Our previous studies showed that addition of polyclonal antimannan IgG to mannan-absorbed NHS containing EGTA produced C3 binding kinetics that were indistinguishable from the kinetics observed with nonabsorbed NHS containing EGTA (17). We further demonstrated IgG-dependent initiation of the alternative pathway by C. albicans using the six purified alternative pathway proteins (17).There are at least three possible explanations for the failure of MAbs B6 and B6.1 to facilitate activation of the alternative pathway. First, it is possible that antimannan antibodies of the IgM class are unable to enhance C3 deposition via the alternative pathway. However, there is evidence that polyclonal IgM is able to enhance alternative pathway-mediated lysis of rabbit erythrocytes by NHS (11, 14). Second, the ability of an antibody to facilitate deposition of C3 via the alternative pathway could be epitope specific; MAbs B6 and B6.1 could have the wrong epitope specificity. As noted above, Eisenberg and Schwab (2) found that polyclonal antibodies specific for one antigen found on group A streptococcal cell walls were able to facilitate initiation of the alternative pathway, whereas antibodies specific for two other antigens were not. If antibody-facilitated activation of the alternative pathway is dependent on epitope specificity, such a finding might influence strategies for induction of protective immunity to Candida. Optimal immunization may require an immunogen that induces antibodies with epitope specificities needed to facilitate activation of the alternative pathway. Finally, we cannot exclude the possibility that human antimannan antibodies are able to facilitate activation of the alternative pathway, whereas mouse antibodies lack this capability.In studies involving a murine model of disseminated candidiasis, MAb B6.1 was shown to be protective, whereas MAb B6 was not (4). However, the protection mechanisms remain to be elucidated. In an in vitro assay, MAb B6.1 but not MAb B6 was found to enhance candidacidal activity of polymorphonuclear leukocytes in the presence of fresh mouse serum, suggesting the involvement of mouse complement in the killing (1). Although assessing the role of complement in MAb B6.1-mediated protection was beyond the scope of this study, our observation that the two antibodies mediate similar kinetics of C3 deposition for C. albicans does not preclude the possibility that the composition and/or accessibility of opsonic complement fragments bound to the yeast cells might differ following complement activation by these two antibodies. Alternatively, the concerted action of several protective functions, including activation of the complement system, may be required for MAb B6.1-mediated protection. 相似文献