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931.
Zohara Sternberg Kailash Chadha Alicia Lieberman Allison Drake David Hojnacki Bianca Weinstock-Guttman Frederick Munschauer 《Journal of neuroinflammation》2009,6(1):28-8
The study is aimed to determine the role of luteolin (3',4',5,7-tetrahydroxyflavone), alone and in combination with human
interferon-beta (IFN-β), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMCs) isolated from
multiple sclerosis (MS) patients. PBMC proliferation in the presence or absence of these drugs was determined and the production
of pro-inflammatory cytokines (IL-1β, TNF-α), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 was
assessed in the culture supernatants. Luteolin reduced, in a dose-dependent manner, the proliferation of PBMCs, and modulated
the levels of IL-1β and TNF-α released by PBMCs in the culture supernatants. Luteolin reduced the MMP-9/TIMP-1 ratio via lowering
MMP-9 production. In the majority of cases, luteolin, when combined with IFN-β, had additive effects in modulating cell proliferation,
IL-1β, TNF-α, MMP-9 and TIMP-1. 相似文献
932.
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936.
The US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. The mechanisms by which these agents provideclinical benefit are not completely understood. However, knowledge of these mechanisms will be crucial for probing human immune responses and tumour biology in order to understand what distinguishes responders from non-responders. The following next steps are necessary: first, the development of immune-monitoring strategies for the identification of relevant biomarkers; second, the establishment of guidelines for the assessment of clinical end points; and third, the evaluation of combination therapy strategies to improve clinical benefit. 相似文献
937.
Babar IA Czochor J Steinmetz A Weidhaas JB Glazer PM Slack FJ 《Cancer biology & therapy》2011,12(10):908-914
miR-155 is a prominent microRNA (miRNA) that regulates genes involved in immunity and cancer-related pathways. miR-155 is overexpressed in lung cancer, which correlates with poor patient prognosis. It is unclear how miR-155 becomes increased in lung cancers and how this increase contributes to reduced patient survival. Here, we show that hypoxic conditions induce miR-155 expression in lung cancer cells and trigger a corresponding decrease in a validated target, FOXO3A. Furthermore, we find that increased levels of miR-155 radioprotects lung cancer cells, while inhibition of miR-155 radiosensitizes these cells. Moreover, we reveal a therapeutically important link between miR-155 expression, hypoxia, and irradiation by demonstrating that anti-miR-155 molecules also sensitize hypoxic lung cancer cells to irradiation. Our study helps explain how miR-155 becomes elevated in lung cancers, which contain extensive hypoxic microenvironments, and demonstrates that inhibition of miR-155 may have important therapeutic potential as a means to radiosensitize hypoxic lung cancer cells. 相似文献
938.
Brett M. Forshey Allison Stewart Amy C. Morrison Hugo G��lvez Claudio Rocha Helvio Astete Dominique Eza Hua-Wei Chen Chien-Chung Chao Joel M. Montgomery David E. Bentzel Wei-Mei Ching Tadeusz J. Kochel 《The American journal of tropical medicine and hygiene》2010,82(4):683-690
A seroprevalence study for IgG antibodies against spotted fever group (SFGR) and typhus group (TGR) Rickettsia among humans and domestic pets was conducted in the city of Iquitos, located in the Amazon basin of Peru. Of 1,195 human sera analyzed, 521 (43.6%) and 123 (10.3%) were positive for SFGR and TGR antibodies, respectively. District of residence and participant age were associated with antibody positivity for both groups, whereas rodent sightings in the home were associated with TGR antibody positivity. Of the 71 canines tested, 42 (59.2%) were positive for SFGR antibodies, and two (2.8%) were positive for TGR antibodies; one active SFGR infection was detected by polymerase chain reaction. An uncharacterized SFGR species was detected in 95.9% (71/74) of Ctenocephalides felis pools collected from domestic pets. These data suggest that rickettsial transmission is widespread in Iquitos. Rickettsia species should be further explored as potential causes of acute febrile illnesses in the region. 相似文献
939.
Randall J. Olsen Izabela Sitkiewicz Ara A. Ayeras Vedia E. Gonulal Concepcion Cantu Stephen B. Beres Nicole M. Green Benfang Lei Tammy Humbird Jamieson Greaver Ellen Chang Willie P. Ragasa Charles A. Montgomery Joiner Cartwright Jr Allison McGeer Donald E. Low Adeline R. Whitney Philip T. Cagle Terry L. Blasdel Frank R. DeLeo James M. Musser 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(2):888-893
Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis (“flesh-eating disease”). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the ΔmtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research. 相似文献
940.
Eugene J. Lengerich Nicole L. Huey Allison D. Clark ACTION Health Cancer Task Force Brenda C. Kluhsman 《Preventing chronic disease》2009,6(2)