首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   12160篇
  免费   869篇
  国内免费   34篇
耳鼻咽喉   137篇
儿科学   343篇
妇产科学   283篇
基础医学   1430篇
口腔科学   187篇
临床医学   1454篇
内科学   2565篇
皮肤病学   130篇
神经病学   1022篇
特种医学   482篇
外国民族医学   1篇
外科学   2063篇
综合类   122篇
一般理论   11篇
预防医学   1044篇
眼科学   213篇
药学   676篇
中国医学   9篇
肿瘤学   891篇
  2023年   116篇
  2022年   253篇
  2021年   557篇
  2020年   283篇
  2019年   400篇
  2018年   468篇
  2017年   341篇
  2016年   360篇
  2015年   452篇
  2014年   604篇
  2013年   644篇
  2012年   1041篇
  2011年   1091篇
  2010年   552篇
  2009年   425篇
  2008年   785篇
  2007年   742篇
  2006年   716篇
  2005年   641篇
  2004年   523篇
  2003年   506篇
  2002年   437篇
  2001年   69篇
  2000年   45篇
  1999年   63篇
  1998年   63篇
  1997年   52篇
  1996年   45篇
  1995年   35篇
  1994年   35篇
  1993年   50篇
  1992年   48篇
  1991年   40篇
  1990年   38篇
  1989年   41篇
  1988年   28篇
  1987年   26篇
  1986年   18篇
  1985年   23篇
  1984年   31篇
  1983年   22篇
  1982年   24篇
  1981年   19篇
  1980年   25篇
  1979年   17篇
  1978年   18篇
  1977年   21篇
  1976年   14篇
  1975年   21篇
  1974年   16篇
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
41.
The development of resistance to chemotherapy by tumor cells remains a constant limitation to the treatment of cancer. Over the last several years, fibroblast growth factor-2 (FGF-2) has emerged as a growth factor that is capable of modifying the sensitivity of normal and tumor cells to anti-cancer drugs. FGF-2 can produce both drug resistance and drug sensitization in different cell types treated with a variety of cytotoxic agents. An understanding of the differential cellular trafficking and biological activities of the multiple FGF-2 isoforms will help in determining the circumstances under which FGF-2 acts to inhibit versus potentiate drug action. Recent advances suggest that expression of FGF-2 in tumor cells is involved with loss of response to chemotherapy in vivo. Thus, the manipulation of FGF-2 activities to increase the effectiveness of chemotherapeutic agents may have important clinical implications.  相似文献   
42.
To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.  相似文献   
43.
OBJECTIVES: Childhood obesity contributes to a wide array of medical conditions, including asthma. There is also increasing evidence in adult patients admitted to the intensive care unit (ICU) that obesity contributes to increased morbidity and to a prolonged length of stay. We hypothesized that obesity is associated with the need for increased duration of therapy in children admitted to the ICU with status asthmaticus. DESIGN: Retrospective cohort study. SETTING: A tertiary pediatric ICU in a university-affiliated children's hospital. PATIENTS: We retrospectively examined data from all children older than 2 yrs admitted to the ICU with status asthmaticus between April 1997 and June 2004. Children were classified as normal weight (<95% weight-for-age percentile) or obese (>95% weight-for-age). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 209 children admitted to the ICU with asthma, 45 (22%) were obese. Compared with children of normal weight, the obese children were older (9.7 +/- 4.4 vs. 8.0 +/- 4.3 yrs, p = .02), more likely to be female (60% vs. 37%, p < .01), and more likely to have been admitted to the ICU previously (40% vs. 20%, p = .01). The obese children also had a statistically significant difference in race (more likely to be Hispanic) and in baseline asthma classification (more likely to have persistent asthma). Despite similar severity of illness at ICU admission, obese children had a significantly longer ICU length of stay (116 +/- 125 hrs vs. 69 +/- 57 hrs, p = .02) and hospital length of stay (9.8 +/- 7.0 vs. 6.5 +/- 3.4 days, p < .01). Obese children also received longer courses of supplemental oxygen, continuous albuterol, and intravenous steroids. CONCLUSIONS: Childhood obesity significantly affects the health of children with asthma. Obese children with status asthmaticus recovered more slowly from an acute exacerbation, even after adjustment for baseline asthma severity and admission severity of illness.  相似文献   
44.
The etiology of acute myeloid leukemia (AML) is relatively unknown. Incidence rates are highest in the agricultural Midwest region compared with other regions of the United States. Many studies have examined the relationship between farming and leukemia, but most have mainly focused on men. We examined the potential association between farm or rural residence and AML in the Iowa Women's Health Study. In 1986, 37,693 women who were free of prior cancer completed a lifestyle and health questionnaire, which included a question on the place of residence. Women were subsequently followed until 2002 for cancer incidence; 79 women developed AML during the time period. Women who lived on a farm at baseline were more likely (relative risk, 1.91; 95% confidence interval, 1.19-3.05) to develop AML compared with women who did not live on a farm. Further, women who reported living on a farm or in a rural area were twice as likely (relative risk, 2.38; 95% confidence interval, 1.33-4.26) to develop AML compared with women who lived in a city with a population of >10,000 people. These results provide evidence that women who live on farms or rural areas are at an increased risk of AML.  相似文献   
45.
The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here, we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated, and disruption of its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site—the FCS, loop length, and glycosylation—are required for efficient SARS-CoV-2 replication and pathogenesis.

SARS-CoV-2 emerged in late 2019 and has caused the largest pandemic since the 1918 influenza outbreak (1). An unusual feature of SARS-CoV-2 is the presence of a furin cleavage site (FCS) in its spike protein (2). The CoV spike is a trimer of spike proteins composed of the S1 and S2 subunits, responsible for receptor binding and membrane fusion, respectively (1). After receptor binding, the spike protein is proteolytically cleaved at the S1/S2 and S2′ sites to activate the fusion machinery. For SARS-CoV-2, the spike protein contains a novel cleavage motif recognized by the host cell furin protease (PRRAR) directly upstream of the S1/S2 cleavage site that facilitates cleavage prior to virion release from the producer cell. This FCS, not found in other group 2B CoVs, plays a key role in spike processing, infectivity, and pathogenesis as shown by our group and others (3, 4).Importantly, another novel amino acid motif, QTQTN, is found directly upstream of the FCS. This QTQTN motif, also absent in other group 2B CoVs, is often deleted and has been pervasive in cultured virus stocks of the alpha, beta, and delta variants (58). In addition, the QTQTN deletion has been observed in a small subset of patient samples as well (911). Because this deletion has been frequently identified, we set out to characterize it and determine whether it has consequences for viral replication and virulence. Using our infectious clone (12, 13), we demonstrated that the loss of this motif attenuates SARS-CoV-2 replication in respiratory cells in vitro and pathogenesis in hamsters. The QTQTN deletion results in reduced spike cleavage and diminished capacity to use serine proteases on the cell surface for entry. Importantly, mutations of glycosylation-enabling residues in the QTQTN motif results in similar replication attenuation despite intact spike processing. Together, our results highlight elements in the SARS-CoV-2 spike in addition to the FCS that contribute to increased replication and pathogenesis.  相似文献   
46.
Purpose of ReviewThe role of the meniscus in preserving the biomechanical function of the knee joint has been clearly defined. The hypothesis that meniscus root integrity is a prerequisite for meniscus function is supported by the development of progressive knee osteoarthritis (OA) following meniscus root tears (MRTs) treated either non-operatively or with meniscectomy. Consequently, there has been a resurgence of interest in the diagnosis and treatment of MRTs. This review examines the contemporary literature surrounding the natural history, clinical presentation, evaluation, preferred surgical repair technique and outcomes.Recent FindingsSurgeons must have a high index of suspicion in order to diagnose a MRT because of the nonspecific clinical presentation and difficult visualization on imaging. Compared with medial MRTs that commonly occur in middle age/older patients, lateral meniscus root injuries tend to occur in younger males with lower BMIs, less cartilage degeneration, and with concomitant ligament injury. Subchondral insufficiency fractures of the knee have been found to be associated with both MRTs and following arthroscopic procedures. Meniscus root repair has demonstrated good outcomes, and acute injuries with intact cartilage should be repaired. Cartilage degeneration, BMI, and malalignment are important considerations when choosing surgical candidates. Meniscus centralization has emerged as a viable adjunct strategy aimed at correcting meniscus extrusion.SummaryMeniscus root repair results in a decreased rate of OA and arthroplasty and is economically advantageous when compared with nonoperative treatment and partial meniscectomy. The transtibial pull-through technique with the addition of centralization for the medial meniscus is associated with encouraging early results.  相似文献   
47.
Background We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide.Methods We used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week in unselected patients with solid tumours.Results Twenty (8 male, 12 female) patients with various solid tumours were treated (18 evaluable for toxicity) over eight planned dose levels (10–300 mg). ALM201 was well-tolerated at all dose levels without CTCAE grade 4 toxicities. Adverse events were predominantly grades 1–2, most commonly, localised injection-site reactions (44.4%), vomiting (11%), fatigue (16.7%), arthralgia (5.6%) and headache (11%). Thrombosis occurred in two patients at the 100 mg and 10 mg dose levels. The MTD was not reached, and a recommended Phase II dose (RP2D) based on feasibility was declared. Plasma exposure increased with dose (less than dose-proportional at the two highest dose levels). No peptide accumulation was evident. The median treatment duration was 11.1 (range 3–18) weeks. Four of 18 evaluable patients (22%) had stable disease.Conclusions Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers.Subject terms: Drug development, Drug safety  相似文献   
48.
A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum.  相似文献   
49.
50.
OBJECTIVE: To determine the utility of screening for depression in pregnant women with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Women with HIV infection who received prenatal care at an inner-city institution between March 2004 and March 2006 were offered the Beck Depression Inventory (BDI), a screening tool to detect depressive symptomatology. Scores >9 were considered positive. RESULTS: Of 51 subjects who participated, 53% had positive screening scores for depression. Of those whose scores were positive, 33% had no prior history of psychiatric illness. Those in whom HIV was diagnosed during pregnancy had higher mean and median BDI scores than those with HIV diagnosed before pregnancy (21.2 vs. 13.3 and 21 vs. 9.5, respectively; p = 0.049). Two factors were associated with positive screenings: history of psychiatric disease (p = 0.001) and history of substance abuse (p = 0.042). Patients with positive screenings first presented for prenatal care at a later gestational age and had fewer prenatal visits than those without evidence of depression (14.9 vs. 12.0, p = 0.035 and 9.2 vs. 11.3, p = 0.045). More than half (56%) who screened positive received psychological care during the prenatal period. CONCLUSION: Women with HIV infection should routinely be screened for depression during pregnancy. Those with positive screens should be offered formal psychological evaluation.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号