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971.
Kihyun Kim Sun‐Young Kong Mariateresa Fulciniti Xianfeng Li Weihua Song Sabikun Nahar Peter Burger Mathew J. Rumizen Klaus Podar Dharminder Chauhan Teru Hideshima Nikhil C. Munshi Paul Richardson Ann Clark Janet Ogden Andreas Goutopoulos Luca Rastelli Kenneth C. Anderson Yu‐Tzu Tai 《British journal of haematology》2010,149(4):537-549
This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine‐induced osteoclast differentiation more potently (9‐ to 10‐fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G0‐G1 cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib, rapamycin) anti‐MM therapies. Significant tumour growth reduction in AS703026‐ vs. vehicle‐treated mice bearing H929 MM xenograft tumours correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels in vivo. Moreover, AS703026 (<200 nmol/l) was cytotoxic against the majority of tumour cells tested from patients with relapsed and refractory MM (84%), regardless of mutational status of RAS and BRAF genes. Importantly, BMSC‐induced viability of MM patient cells was similarly blocked within the same dose range. Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti‐MM agents, to improve patient outcome. 相似文献
972.
973.
Robert J. A. Frost F. Kent Hamra James A. Richardson Xiaoxia Qi Rhonda Bassel-Duby Eric N. Olson 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(26):11847-11852
Piwi-interacting RNAs (piRNAs) comprise a broad class of small noncoding RNAs that function as an endogenous defense system against transposable elements. Here we show that the putative DExD-box helicase MOV10-like-1 (MOV10L1) is essential for silencing retrotransposons in the mouse male germline. Mov10l1 is specifically expressed in germ cells with increasing expression from gonocytes/type A spermatogonia to pachytene spermatocytes. Primary spermatocytes of Mov10l1−/− mice show activation of LTR and LINE-1 retrotransposons, followed by cell death, causing male infertility and a complete block of spermatogenesis at early prophase of meiosis I. Despite the early expression of Mov10l1, germline stem cell maintenance appears unaffected in Mov10l1−/− mice. MOV10L1 interacts with the Piwi proteins MILI and MIWI. MOV10L1 also interacts with heat shock 70-kDa protein 2 (HSPA2), a testis-enriched chaperone expressed in pachytene spermatocytes and also essential for male fertility. These studies reveal a crucial role of MOV10L1 in male fertility and piRNA-directed retrotransposon silencing in male germ cells and suggest that MOV10L1 functions as a key component of a safeguard mechanism for the genetic information in male germ cells of mammals. 相似文献
974.
Marquis S Hawkins Kristi L Storti Caroline R Richardson Wendy C King Scott J Strath Robert G Holleman Andrea M Kriska 《The international journal of behavioral nutrition and physical activity》2009,6(1):31-7
Background
Accelerometers were incorporated in the 2003–2004 National Health and Nutritional Examination Survey (NHANES) study cycle for objective assessment of physical activity. This is the first time that objective physical activity data are available on a nationally representative sample of U.S. residents. The use of accelerometers allows researchers to measure total physical activity, including light intensity and unstructured activities, which may be a better predictor of health outcomes than structured activity alone. The aim of this study was to examine objectively determined physical activity levels by sex, age and racial/ethnic groups in a national sample of U.S. adults. 相似文献975.
Jo M. Martin Jessica M. Ghaferi Deborah L. Cummins Adam J. Mamelak Chrys D. Schmults Mona Parikh Lark-Aeryn Speyer Alice Chuang Hazel V. Richardson David Stein Nanette J. Liégeois 《American journal of public health》2009,99(12):2140-2146
Historical reviews suggest that tanning first became fashionable in the 1920s or 1930s. To quantitatively and qualitatively examine changes in tanning attitudes portrayed in the popular women''s press during the early 20th century, we reviewed summer issues of Vogue and Harper''s Bazaar for the years 1920, 1927, 1928, and 1929. We examined these issues for articles and advertisements promoting skin tanning or skin bleaching and protection. We found that articles and advertisements promoting the fashionable aspects of tanned skin were more numerous in 1928 and 1929 than in 1927 and 1920, whereas those promoting pale skin (by bleaching or protection) were less numerous. These findings demonstrate a clear shift in attitudes toward tanned skin during this period.NUMEROUS STUDIES HAVE linked exposure to ultraviolet (UV) light to both melanoma1–4 and nonmelanoma skin cancers.2–4 The incidence of skin cancers has risen dramatically over the past century,5–7 and this is largely attributed to increased exposure to UV light from the sun. Despite public education initiatives aimed at preventing skin cancer,8 many individuals continue to tan, citing such reasons as the relationship between tanning and physical and emotional health, an active lifestyle, and physical beauty.9From a historical perspective, tanning as a fashion trend is a relatively new phenomenon, first noted in the 20th century. Earlier, pale skin was often perceived as a mark of beauty, wealth, and refinement, whereas tanned skin was considered to be typical of manual laborers.10 In the early 20th century, European and American women took precautions to maintain a light skin tone. Parasols and large hats were considered essential summer accessories.11 Magazines in the early 20th century advertised powders that would conceal a tan as well as numerous bleach treatments, such as Bleachine Cream, which was featured in an advertisement by Elizabeth Arden in the July 1, 1920, issue of Vogue as “A mild but effective preparation for removing tan. Nourishing as well as whitening. Excellent for the hands.”12 Toxic lead-based cosmetics, which date back to ancient Roman society, and other types of body powders were commonly used to lighten and augment fair skin during this era.9,13Although it is well-known that social attitudes changed from sun protection to sun seeking during the first half of the 20th century, the exact year for such a cultural shift has remained obscure. Previous reviews on this subject suggest that the trend began in the late 1920s or early 1930s.10,14 Magazines from the late 1920s reflect a clear shift in attitude, as illustrated in an article from a 1929 issue of Harper''s Bazaar: “Shall We Gild the Lily? There Is a Technique to a Good Tan—Whether by Fair Means or Fake!”15Open in a separate windowOpen in a separate windowJantzen swimsuit advertisement from (a) 1927 showing models with sun protection, including shawls, parasols, and wide-brimmed hats, and (b) 1929 depicting models in similar bathing suits, but now frolicking in the sun without sun protection.Illustrations by Frank Clark. Reprinted with permission of Jantzen. 相似文献
976.
Dana Loomis Michael D. Schulman A. John Bailer Kevin Stainback Matthew Wheeler David B. Richardson Stephen W. Marshall 《American journal of public health》2009,99(8):1400-1408
Objectives. We investigated the extent to which the political economy of US states, including the relative power of organized labor, predicts rates of fatal occupational injury.Methods. We described states’ political economies with 6 contextual variables measuring social and political conditions: “right-to-work” laws, union membership density, labor grievance rates, state government debt, unemployment rates, and social wage payments. We obtained data on fatal occupational injuries from the National Traumatic Occupational Fatality surveillance system and population data from the US national census. We used Poisson regression methods to analyze relationships for the years 1980 and 1995.Results. States differed notably with respect to political–economic characteristics and occupational fatality rates, although these characteristics were more homogeneous within rather than between regions. Industry and workforce composition contributed significantly to differences in state injury rates, but political–economic characteristics of states were also significantly associated with injury rates, after adjustment accounting for those factors.Conclusions. Higher rates of fatal occupational injury were associated with a state policy climate favoring business over labor, with distinct regional clustering of such state policies in the South and Northeast.Workers in the United States have experienced a sustained decline in the rate of fatal occupational injury over the past decades, yet there are marked differences in fatal injury rates and trends among regions and states.1–5 In the final decades of the 20th century, for example, the average annual rate for all fatal occupational injuries ranged from 1.7 per 100 000 in Connecticut to 24.3 per 100 000 in Alaska; the average rate of decline varied from less than 1% per year in the Northeast to almost 5% per year in the West.3,4 The causes of geographical diversity in occupational injury rates are largely unknown.The spatial variation in natural resources, topography, and climate that condition the kinds of work available in a state or region offer one possible explanation for spatial differences in fatal occupational injury rates. Another explanation for this diversity derives from consideration of government policy on economic development and labor, which can influence where employers locate, how they operate, and the attention they give to worker safety.6 Some factors common to areas with high rates of fatal occupational injury can be observed. Within the United States, it has been noted that higher fatal injury rates are concentrated in the Western and Southern regions, in rural areas, and in less wealthy states.7,8The embeddedness of industries and jobs in local conditions implies that the local political–economic structure has an important effect on occupational injury rates. We reasoned that variation in the strength of labor unions, state welfare provisions, and unemployment levels influences the ability of labor to secure better-paying and safer jobs.9 As jobs in traditional manufacturing decrease,10,11 declining unionization rates, contracting social welfare programs, and increasing capital mobility change the balance of power between capital and labor.12 In addition, states’ capacity to monitor and regulate health and occupational safety depends on their fiscal health and their strategies for creating an economic climate conducive to capitalist development and growth.13 The role of states has increased since the 1980s with the rise of the “New Federalism” in US government, which devolved functions once performed by the federal government to state and local jurisdictions.14No formal analyses of these patterns have been conducted for a number of years,15 and states’ economic characteristics and policies have been neglected as potential determinants of geographic variation in occupational injury rates. We examined relationships between fatal occupational injury rates and political–economic characteristics of US states to learn whether fatal occupational injury rates are associated with state political economy after accounting for variation in economic structure and labor force composition. We expected that in states where the capacity of labor is stronger (higher union density), the rate of fatal occupational injury would be lower. We expected states with greater labor market deregulation (e.g., so-called right-to-work laws, which limit labor''s ability to organize) to have a higher incidence of fatal injury because of the reduction in the relative power of labor. We also hypothesized that high state debt would be associated with a higher risk of occupational fatality, although one could argue that state debt may also accrue as a result of investment in public infrastructure or social services that reduce the risk of injury or increase the bargaining power of labor. 相似文献
977.
Clifford P. Weisel Susan D. Richardson Benoit Nemery Gabriella Aggazzotti Eugenio Baraldi Ernest R. Blatchley III Benjamin C. Blount Kai-H?kon Carlsen Peyton A. Eggleston Fritz H. Frimmel Michael Goodman Gilbert Gordon Sergey A. Grinshpun Dirk Heederik Manolis Kogevinas Judy S. LaKind Mark J. Nieuwenhuijsen Fontaine C. Piper Syed A. Sattar 《Environmental health perspectives》2009,117(4):500-507
Objectives
Recent studies have explored the potential for swimming pool disinfection by-products (DBPs), which are respiratory irritants, to cause asthma in young children. Here we describe the state of the science on methods for understanding children’s exposure to DBPs and biologics at swimming pools and associations with new-onset childhood asthma and recommend a research agenda to improve our understanding of this issue.Data sources
A workshop was held in Leuven, Belgium, 21–23 August 2007, to evaluate the literature and to develop a research agenda to better understand children’s exposures in the swimming pool environment and their potential associations with new-onset asthma. Participants, including clinicians, epidemiologists, exposure scientists, pool operations experts, and chemists, reviewed the literature, prepared background summaries, and held extensive discussions on the relevant published studies, knowledge of asthma characterization and exposures at swimming pools, and epidemiologic study designs.Synthesis
Childhood swimming and new-onset childhood asthma have clear implications for public health. If attendance at indoor pools increases risk of childhood asthma, then concerns are warranted and action is necessary. If there is no such relationship, these concerns could unnecessarily deter children from indoor swimming and/or compromise water disinfection.Conclusions
Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists. 相似文献978.
Sapsford RR Richardson CA Maher CF Hodges PW 《Archives of physical medicine and rehabilitation》2008,89(9):1741-1747
Sapsford RR, Richardson CA, Maher CF, Hodges PW. Pelvic floor muscle activity in different sitting postures in continent and incontinent women.
Objective
To determine whether resting activity of the pelvic floor muscles (PFMs) and abdominal muscles varied in different sitting postures in parous women with and without stress urinary incontinence (SUI).Design
PFM and abdominal muscle activity was recorded in 3 sitting postures: slump supported, upright unsupported, and very tall unsupported. Spinal curves were measured in slump supported and upright unsupported.Setting
A research laboratory.Participants
Women (N=17) with a history of vaginal delivery, 8 who were symptomatic of SUI and 9 who were asymptomatic.Interventions
Not applicable.Main Outcome Measures
Electromyographic activity of (1) the resting PFM recorded per vaginam with surface electrodes and (2) superficial abdominal muscles using surface electrodes. Changes in spinal curves were measured with a flexible ruler.Results
Electromyographic activity of the PFM increased significantly from slump supported to upright unsupported postures in both groups (P<.001) but with lower levels of activity in women with SUI (P<.05). PFM activity increased further in very tall unsupported sitting in comparison with slump supported sitting (P<.001). Obliquus internus abdominis electromyographic activity was greater in upright unsupported than in slump supported sitting (P<.05), and electromyographic activity of other abdominal muscles was greater in very tall unsupported than slump supported. Women with SUI had a trend for greater activity in the abdominal muscles in upright unsupported than asymptomatic women. Asymptomatic women had a greater depth of lumbar lordosis in upright unsupported sitting than women with SUI (P=.04).Conclusions
More upright sitting postures recruit greater PFM resting activity irrespective of continence status. Further investigation should consider the effect of sitting posture in rehabilitation. 相似文献979.
Richardson DB 《American journal of epidemiology》2009,169(1):78-85
A simple SAS software program (SAS Institute, Inc., Cary, NorthCarolina) was developed for fitting an exact formulation ofthe 2-stage clonal expansion model accommodating piecewise constantexposures and left and right censoring of observations. Dataon leukemia mortality and occupational exposure to benzene amongrubber hydrochloride production workers in Ohio (1940–1996)were analyzed by using this approach. A model in which benzeneexposure increased clonal expansion fit these data well; littleevidence of an association between benzene exposure and initiationof leukemia was found. The estimated exposure-response associationincreased in magnitude with age at exposure and decreased withtime since exposure. This analysis shows that the 2-stage clonalexpansion model can be readily fit to epidemiologic cohort databy using a simple SAS program. The illustrative analyses ofleukemia mortality among rubber hydrochloride workers suggestthat the effect of benzene on leukemia risk is due to an exposure-inducedincrease in the proliferation of initiated cells. benzene; leukemia; models, statistical 相似文献
980.
Goodman M Almon L Bayakly R Butler S Crosby C DiIorio C Ekwueme D Fletcher D Fowler J Gillespie T Glanz K Hall I Lee J Liff J Lipscomb J Pollack LA Richardson LC Roberts P Steenland K Ward K 《Journal of community health》2009,34(1):23-32
Whereas, most cancer research data come from high-profile academic centers, little is known about the outcomes of cancer care in rural communities. We summarize the experience of building a multi-institution partnership to develop a cancer outcomes research infrastructure in Southwest Georgia (SWGA), a primarily rural 33-county area with over 700,000 residents. The partnership includes eight institutions: the Emory University in Atlanta, the Centers for Disease Control and Prevention (CDC), the Georgia Comprehensive Center Registry (the Registry), the Southwest Georgia Cancer Coalition (the Coalition), and the four community cancer centers located within the SWGA region. The practical application of the partnership model, its organizational structure, and lessons learned are presented using two specific examples: a study evaluating treatment decisions and quality of life among prostate cancer patients, and a study of treatment discontinuation among prostate, breast, lung, and colorectal cancer patients. Our partnership model allowed us to (1) use the Coalition as a link between Atlanta-based researchers and local community; (2) collaborate with the area cancer centers on day-to-day study activities; (3) involve the Registry personnel and resources to identify eligible cancer cases and to perform data collection; and (4) raise community awareness and sense of study ownership through media announcements organized by the Coalition. All of the above activities were performed in consultation with the funding institution (CDC) and its project directors who oversee several other studies addressing similar research questions throughout the country. Our partnership model may provide a useful framework for cancer outcomes research projects in rural communities. 相似文献