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71.
P J Gatti K J Hill A M Da Silva W P Norman R A Gillis 《The Journal of pharmacology and experimental therapeutics》1988,245(1):373-380
The purpose of our study was to determine whether clonidine exerts its centrally mediated hypotensive action at three sites that influence arterial pressure located in the medulla, specifically associated with the intermediate area of the ventrolateral medulla. The "intermediate area" lies approximately 1.5 mm caudal to the border of the trapezoid body (caudal border) and 4 mm lateral to the midline. One of the sites that influence arterial pressure lies in the nucleus reticularis rostroventrolateralis. The second site lies in close proximity to the rostral part of the nucleus reticularis lateralis (rLRN) and also near the A1 area. The third site lies in the most rostral area and medial to the nucleus reticularis rostroventrolateralis, that is in the nucleus paragigantocellularis lateralis. Unilateral microinjections of 0.22 and 0.43 nmol of clonidine into the rLRN produced dose-dependent decreases in arterial pressure. The 0.43 nmol dose of clonidine had no effect when unilaterally or bilaterally microinjected into either the nucleus reticularis rostroventrolateralis or into the nucleus paragigantocellularis lateralis. Microinjection of the alpha-2 adrenoceptor antagonist, idazoxan (16.6 nmol), unilaterally into rLRN had no effect per se, but prevented the hypotensive effect of a subsequent microinjection of clonidine. Similarly, bilateral microinjection of idazoxan into rLRN counteracted the hypotensive effect of i.v. administered clonidine. These data indicate that clonidine acts at alpha-2 adrenoceptors in the rLRN to produce hypotension. 相似文献
72.
The ability of thiols to reduce 3-azidothymidine (AZT) to 3-aminothymidine has been investigated. Incubation with glutathione, dithiothreitol (DTT), or mercaptoethanol at pH 7.2 and 37°C leads to quantitative reduction of the azido moiety to an amine. The reaction is first order in AZT and first order in reducing agent (mono- or dithiol). The second-order rate constants are 2.77 × 10–3, 6.55 × 10–5, and 6.35 × 10–6
M
–l sec–1 for the dithiothreitol, glutathione, and mercaptoethanol reductions, respectively. The thiol reduction of alkyl azide to amine under mild conditions is a synthetic method particularly suitable for water-soluble azido compounds that are sensitive to catalytic hydrogenation. The potential for the mono- or dithiol-mediated reduction of alkyl azides under biological conditions must be considered when conducting studies of azido drugs. 相似文献
73.
Norman Tinanoff Mary A. Manwell Ricki L. Zameck Joseph E. Grasso 《Journal of clinical periodontology》1989,16(5):284-290
61 adults, with fixed or removable dental protheses, completed a 6-month double-blind trial comparing the clinical and microbial effects of brushing twice daily with either 0.22% NaF or 0.4% SnF2. Those subjects brushing with SnF2 had less gingivitis and fewer bleeding sites for both "total teeth" and "abutment teeth". Plaque scores between groups were only statistically different for the "abutment teeth". The microbial parameters, salivary S. mutans and subgingival plaque total CFU, were significantly reduced in the SnF2 group. In both treatment groups, there was a reduction over the course of the study in the number of subjects with recoverable A. actinomycetemcomitans and black pigmented bacteroides, yet there was no difference between groups. 相似文献
74.
Norman B. Epstein 《Clinical psychology》2005,12(2):139-143
Clinical interventions for extramarital involvement (EMI) have outpaced empirical knowledge about both risk factors for infidelity and effective treatments. Allen et al. (this issue) provide a systematic review of current knowledge organized around stages of the development of EMI and factors concerning the involved partner, the spouse, the couple's relationship, and the interpersonal context. Their review identifies significant gaps in knowledge for which research is needed. Because EMI has multiple determinants, conceptual models and research on it must be multivariate. This comment focuses on priorities for increasing knowledge about EMI, including (a) clarification of variation in definitions and personal standards for EMI through consideration of participants' subjective experiences as well as the views of outsiders (researchers, clinicians); (b) improved qualitative research using interview methods designed to minimize biased questioning by investigators and biased reporting by subjects, to tap individuals' internal experiences with the developmental process of EMI; (c) nonblaming research on characteristics of the noninvolved spouse and the couple's interaction that predict EMI; and (d) adaptation of generic preventive and relationship enrichment interventions for couples involving communication skill-building and psychoeducation, to include information about ways to "inoculate" relationships against commonly unexpected risks of EMI. 相似文献
75.
Identification and characterization of clonal NK-like cells from channel catfish (Ictalurus punctatus) 总被引:1,自引:0,他引:1
Shen L Stuge TB Bengtén E Wilson M Chinchar VG Naftel JP Bernanke JM Clem LW Miller NW 《Developmental and comparative immunology》2004,28(2):139-152
TcR alpha, beta, and gamma chain negative cytotoxic NK-like cells were cloned from alloantigen-stimulated PBL obtained from nai;ve channel catfish. Stimulation with allogeneic cells and growth promoting factors are required for their continued in vitro proliferation and cytotoxic activity. These granular cells kill not only the stimulating allogeneic cells, but also unrelated allogeneic targets by a perforin/granzyme-mediated apoptosis pathway. In addition, they are negative for markers that define neutrophils, monocytes/macrophages, and non-specific cytotoxic cells. Although these NK-like clones kill a number of different allogeneic targets, they display interclonal variation in cytotoxicity toward a panel of allogeneic targets, i.e. some clones have no apparent target specificity, while others display a target preference. In addition, flow cytometric analyses revealed that expression of a putative FcmuR, an LFA-1-like molecule, and a putative thymocyte/T cell antigen varies among the different clones, with no clear correlation between surface antigen expression and cytotoxic activity. Although not all clones express a putative FcmuR, it was noted that they all expressed an ITAM containing FcepsilonR gamma chain homolog. This finding suggests that the catfish FcepsilonR gamma chain may potentially be used as an accessory molecule for not only FcmuRs, but also for other unknown activation receptors. These results support the hypothesis that catfish NK-like cells are heterogeneous in terms of target specificities and cell surface phenotype. 相似文献
76.
Aaron Ettenberg André Laferrière Peter M. Milner Norman White 《Physiology & behavior》1981,27(4):641-647
The hypothesis that responding contributes to the reward value of brain stimulation was tested in two novel experimental paradigms. In the first experiment rats lever-presssed for rewarding brain stimulation during 90 sec periods. After each period the lever automatically retracted and experimenter-administered stimulation (EAS) was presented at the same rate and current parameters as during the self-stimulation (SS). The rats could demonstrate a preference for SS (vs EAS) by pressing a reset lever on the opposite wall of the test chamber. This action terminated the EAS and reinstated the SS-lever for an additional 90 sec. Results showed that the rats preferred to respond for stimulation than to have that same stimulation administered by the experimenter. This was true even when a signal preceded each train of EAS or when subjects had a great deal of previous EAS experience. In the second experiment conditioned taste preferences were observed following novel taste/SS pairings but not following novel taste/EAS pairings. The data from these two experiments suggest that responding contributes to the rewarding value of brain stimulation. 相似文献
77.
With the rise in chronic, behavior-related disease, computerized behavioral protocols (CBPs) that help individuals improve behaviors have the potential to play an increasing role in the future health of society. To be effective and widely used CBPs should be based on accepted behavioral theory. However, designing CBPs while at the same time specifying their linkages to behavioral theory and developing reusable CBP components (interventions) are challenges to developers of CBPs. Having an ontology with which to describe CBPs could help with these issues. As a first step towards creating such an ontology, we modeled PACE-Adolescent, a theory-based behavioral protocol that uses the Stages of Change Model and Social Cognitive Theory, using PROTEGE-2000, an ontology editor and knowledge acquisition system. We created a three-part knowledge model. Two sub-ontologies described behavioral interventions and psychological theories. The third component, implemented using Guideline Interchange Format (GLIF3), provided a way to describe the structure of a protocol and to link intervention resources and groups of actions to elements of psychological theory. Using this framework, we formally described the PACE-Adolescent protocol. Creating knowledge models such as this may lead to improvements in the design and evaluation of computerized health behavior protocols. 相似文献
78.
Malamachanahalli B. Vasudevachari Norman P. Salzman Daniel R. Woll Christopher Mast Katharina W. Uffelman Gary Toedter David Hoefheinz Julie A. Metcalf H. Clifford Lane 《Journal of clinical immunology》1993,13(3):185-192
The presence of p24 core antigen in the serum of individuals with human acquired immunodeficiency syndrome has been used as one of the important prognostic markers of HIV-1 infection and also as an end point in evaluating antiviral drugs and vaccines. Unfortunately the majority of p24 antigen present in serum exists as an antigenantibody complex and is not detected with the commercial kits currently available to measure p24 antigen. In this study, we report a simple procedure utilizing treatment of serum samples with glycine buffer (pH 1.85) to dissociate antigen-antibody complexes prior to assaying for p24 antigen. A 300% increase in the number of p24-reactive samples and a 3- to 12-fold increase in the quantity of antigen detected were observed when samples were pretreated with 1.5M glycine buffer (pH 1.85) for 1 hr. Glycine treatment of samples did not result in nonspecific positive tests and samples previously shown to be reactive remained positive. In reconstruction experiments the release of antigen was found to be inversely proportional to the amount of p24 antibody present in the serum. The percentage of HIV-1-infected patients positive for p24 antigen was clearly a function of CD4 count. Forty-nine percent of patients with more than 500 CD4 cells and 100% of patients with less than 200 CD4 were p24 positive. The improved sensitivity for detection of p24 provided by this procedure enhances our understanding of the pathogenesis of AIDS by showing that the majority of patients with HIV-1 infection is p24 positive and facilitates the analysis of data obtained in clinical trials involving anti-HIV compounds. 相似文献
79.
Abrams DI Bebchuk JD Denning ET Davey RT Fox L Lane HC Sampson J Verheggen R Zeh D Markowitz NP;Terry Beirn Community Programs for Clinical Research on AIDS 《Journal of acquired immune deficiency syndromes (1999)》2002,29(3):221-231
The effect of intermittent courses of recombinant interleukin-2 (rIL-2) on HIV-1 load in patients receiving combination antiretroviral therapy remains uncertain. CPCRA 059 was an open-label, randomized, multicenter trial in which 511 patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3 who were receiving antiretroviral therapy were assigned to receive no rIL-2 (255 patients [controls]) or subcutaneous rIL-2 in dosages of 4.5 MIU (130) or 7.5 MIU (126) twice daily for 5-day courses every 8 weeks to maintain CD4+ cell counts that were twice the baseline value or > or = 1,000/mm3. The primary objective of this study was to compare the effects of the two doses of rIL-2 and no rIL-2 on viral load and CD4+ cell counts over 12 months. There was no difference in the following viral load measurements between the rIL-2 treatment groups and the control treatment group: percentage of patients with viral loads of <50 copies/mL at 12 months (p =.55), time to viral load of > or = 50 copies/mL for patients who had baseline viral loads of <50 copies/mL (p =.35), and change in viral load from baseline for patients who had viral loads of > or = 50 copies/mL at baseline (p =.63). At each follow-up visit, the change in CD4+ cell count from baseline was significantly greater in the rIL-2 treatment groups than in the control treatment group, with a mean difference of 251/mm3 at month 12 (95% confidence interval, 207-295; p <.0001). No unanticipated adverse experiences were seen in this trial, to our knowledge the largest randomized evaluation of rIL-2 treatment conducted to date. 相似文献